1932

Abstract

T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcription factor networks in which these E proteins are embedded are different both in membership and in architecture for T and B cell gene regulatory programs. These differences permit lineage commitment decisions to be made in different hierarchical orders. Furthermore, in contrast to B cell gene networks, the T cell gene network architecture for effector differentiation is sufficiently modular so that E protein inputs can be removed. Complete T cell–like effector differentiation can proceed without T cell receptor rearrangement or selection when E proteins are neutralized, yielding natural killer and other innate lymphoid cells.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-032712-100024
2014-03-21
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/immunol/32/1/annurev-immunol-032712-100024.html?itemId=/content/journals/10.1146/annurev-immunol-032712-100024&mimeType=html&fmt=ahah

Literature Cited

  1. Bajoghli B, Aghaallaei N, Hess I, Rode I, Netuschil N. 1.  et al. 2009. Evolution of genetic networks underlying the emergence of thymopoiesis in vertebrates. Cell 138:186–97 [Google Scholar]
  2. Ramirez J, Lukin K, Hagman J. 2.  2010. From hematopoietic progenitors to B cells: mechanisms of lineage restriction and commitment. Curr. Opin. Immunol. 22:177–84 [Google Scholar]
  3. Zandi S, Bryder D, Sigvardsson M. 3.  2010. Load and lock: the molecular mechanisms of B-lymphocyte commitment. Immunol. Rev. 238:47–62 [Google Scholar]
  4. Mandel EM, Grosschedl R. 4.  2010. Transcription control of early B cell differentiation. Curr. Opin. Immunol. 22:161–67 [Google Scholar]
  5. Cobaleda C, Schebesta A, Delogu A, Busslinger M. 5.  2007. Pax5: the guardian of B cell identity and function. Nat. Immunol. 8:463–70 [Google Scholar]
  6. Matthias P, Rolink AG. 6.  2005. Transcriptional networks in developing and mature B cells. Nat. Rev. Immunol. 5:497–508 [Google Scholar]
  7. Thompson PK, Zúñiga-Pflücker JC. 7.  2011. On becoming a T cell, a convergence of factors kick it up a Notch along the way. Semin. Immunol. 23:350–59 [Google Scholar]
  8. Naito T, Tanaka H, Naoe Y, Taniuchi I. 8.  2011. Transcriptional control of T-cell development. Int. Immunol. 23:661–68 [Google Scholar]
  9. Love PE, Bhandoola A. 9.  2011. Signal integration and crosstalk during thymocyte migration and emigration. Nat. Rev. Immunol. 11:469–77 [Google Scholar]
  10. Yang Q, Bell JJ, Bhandoola A. 10.  2010. T-cell lineage determination. Immunol. Rev. 238:12–22 [Google Scholar]
  11. Rothenberg EV, Zhang J, Li L. 11.  2010. Multilayered specification of the T-cell lineage fate. Immunol. Rev. 238:150–68 [Google Scholar]
  12. Rothenberg EV, Moore JE, Yui MA. 12.  2008. Launching the T-cell-lineage developmental programme. Nat. Rev. Immunol. 8:9–21 [Google Scholar]
  13. Petrie HT, Zúñiga-Pflücker JC. 13.  2007. Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu. Rev. Immunol. 25:649–79 [Google Scholar]
  14. Ding L, Morrison SJ. 14.  2013. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495:231–35 [Google Scholar]
  15. Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ. 15.  et al. 2013. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495:227–30 [Google Scholar]
  16. Sitnicka E, Buza-Vidas N, Ahlenius H, Cilio CM, Gekas C. 16.  et al. 2007. Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors. Blood 110:2955–64 [Google Scholar]
  17. Dolence JJ, Gwin K, Frank E, Medina KL. 17.  2011. Threshold levels of Flt3-ligand are required for the generation and survival of lymphoid progenitors and B-cell precursors. Eur. J. Immunol. 41:324–34 [Google Scholar]
  18. Narayan K, Sylvia KE, Malhotra N, Yin CC, Martens G. 18.  et al. 2012. Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes. Nat. Immunol. 13:511–18 [Google Scholar]
  19. Kreslavsky T, Gleimer M, Garbe AI, von Boehmer H. 19.  2010. αβ versus γδ fate choice: counting the T-cell lineages at the branch point. Immunol. Rev. 238:169–81 [Google Scholar]
  20. Bonneville M, O'Brien RL, Born WK. 20.  2010. γδ T cell effector functions: a blend of innate programming and acquired plasticity. Nat. Rev. Immunol. 10:467–78 [Google Scholar]
  21. Taghon T, Rothenberg EV. 21.  2008. Molecular mechanisms that control mouse and human TCR-αβ and TCR-γδ T cell development. Semin. Immunopathol. 30:383–98 [Google Scholar]
  22. Xiong N, Raulet DH. 22.  2007. Development and selection of γδ T cells. Immunol. Rev. 215:15–31 [Google Scholar]
  23. Hsieh CS, Lee HM, Lio CW. 23.  2012. Selection of regulatory T cells in the thymus. Nat. Rev. Immunol. 12:157–67 [Google Scholar]
  24. Wirnsberger G, Hinterberger M, Klein L. 24.  2011. Regulatory T-cell differentiation versus clonal deletion of autoreactive thymocytes. Immunol. Cell Biol. 89:45–53 [Google Scholar]
  25. Alonzo ES, Sant'Angelo DB. 25.  2011. Development of PLZF-expressing innate T cells. Curr. Opin. Immunol. 23:220–27 [Google Scholar]
  26. Carpenter AC, Bosselut R. 26.  2010. Decision checkpoints in the thymus. Nat. Immunol. 11:666–73 [Google Scholar]
  27. Naito T, Taniuchi I. 27.  2010. The network of transcription factors that underlie the CD4 versus CD8 lineage decision. Int. Immunol. 22:791–96 [Google Scholar]
  28. He X, Park K, Kappes DJ. 28.  2010. The role of ThPOK in control of CD4/CD8 lineage commitment. Annu. Rev. Immunol. 28:295–320 [Google Scholar]
  29. Das R, Sant'Angelo DB, Nichols KE. 29.  2010. Transcriptional control of invariant NKT cell development. Immunol. Rev. 238:195–215 [Google Scholar]
  30. Collins A, Littman DR, Taniuchi I. 30.  2009. RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nat. Rev. Immunol. 9:106–15 [Google Scholar]
  31. Schwartzberg PL, Mueller KL, Qi H, Cannons JL. 31.  2009. SLAM receptors and SAP influence lymphocyte interactions, development and function. Nat. Rev. Immunol. 9:39–46 [Google Scholar]
  32. Wang L, Bosselut R. 32.  2009. CD4-CD8 lineage differentiation: Thpok-ing into the nucleus. J. Immunol. 183:2903–10 [Google Scholar]
  33. Singer A, Adoro S, Park JH. 33.  2008. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat. Rev. Immunol. 8:788–801 [Google Scholar]
  34. Yosef N, Shalek AK, Gaublomme JT, Jin H, Lee Y. 34.  et al. 2013. Dynamic regulatory network controlling TH17 cell differentiation. Nature 496:461–68 [Google Scholar]
  35. Ciofani M, Madar A, Galan C, Sellars M, Mace K. 35.  et al. 2012. A validated regulatory network for Th17 cell specification. Cell 151:289–303 [Google Scholar]
  36. Liu X, Yan X, Zhong B, Nurieva RI, Wang A. 36.  et al. 2012. Bcl6 expression specifies the T follicular helper cell program in vivo. J. Exp. Med. 209:1841–52, S1–24 [Google Scholar]
  37. Vahedi G, Takahashi H, Nakayamada S, Sun HW, Sartorelli V. 37.  et al. 2012. STATs shape the active enhancer landscape of T cell populations. Cell 151:981–93 [Google Scholar]
  38. Samstein RM, Arvey A, Josefowicz SZ, Peng X, Reynolds A. 38.  et al. 2012. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell 151:153–66 [Google Scholar]
  39. Wei G, Abraham BJ, Yagi R, Jothi R, Cui K. 39.  et al. 2011. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity 35:299–311 [Google Scholar]
  40. Wei G, Wei L, Zhu J, Zang C, Hu-Li J. 40.  et al. 2009. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30:155–67 [Google Scholar]
  41. Luc S, Luis TC, Boukarabila H, Macaulay IC, Buza-Vidas N. 41.  et al. 2012. The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential. Nat. Immunol. 13:412–19 [Google Scholar]
  42. Doulatov S, Notta F, Eppert K, Nguyen LT, Ohashi PS, Dick JE. 42.  2010. Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat. Immunol. 11:585–93 [Google Scholar]
  43. Kawamoto H, Ikawa T, Masuda K, Wada H, Katsura Y. 43.  2010. A map for lineage restriction of progenitors during hematopoiesis: the essence of the myeloid-based model. Immunol. Rev. 238:23–36 [Google Scholar]
  44. Ng SY, Yoshida T, Zhang J, Georgopoulos K. 44.  2009. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity 30:493–507 [Google Scholar]
  45. Månsson R, Hultquist A, Luc S, Yang L, Anderson K. 45.  et al. 2007. Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors. Immunity 26:407–19 [Google Scholar]
  46. Lai AY, Kondo M. 46.  2007. Identification of a bone marrow precursor of the earliest thymocytes in adult mouse. Proc. Natl. Acad. Sci. USA 104:6311–16 [Google Scholar]
  47. Lai AY, Kondo M. 47.  2006. Asymmetrical lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. J. Exp. Med. 203:1867–73 [Google Scholar]
  48. Perry SS, Welner RS, Kouro T, Kincade PW, Sun XH. 48.  2006. Primitive lymphoid progenitors in bone marrow with T lineage reconstituting potential. J. Immunol. 177:2880–87 [Google Scholar]
  49. Richie Ehrlich LI, Serwold T, Weissman IL. 49.  2011. In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors. Blood 117:2618–24 [Google Scholar]
  50. Schlenner SM, Madan V, Busch K, Tietz A, Laufle C. 50.  et al. 2010. Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus. Immunity 32:426–36 [Google Scholar]
  51. Saran N, Lyszkiewicz M, Pommerencke J, Witzlau K, Vakilzadeh R. 51.  et al. 2010. Multiple extrathymic precursors contribute to T-cell development with different kinetics. Blood 115:1137–44 [Google Scholar]
  52. Serwold T, Ehrlich LI, Weissman IL. 52.  2009. Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis. Blood 113:807–15 [Google Scholar]
  53. Luc S, Anderson K, Kharazi S, Buza-Vidas N, Boiers C. 53.  et al. 2008. Down-regulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential. Blood 111:3424–34 [Google Scholar]
  54. Adolfsson J, Månsson R, Buza-Vidas N, Hultquist A, Liuba K. 54.  et al. 2005. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential: a revised road map for adult blood lineage commitment. Cell 121:295–306 [Google Scholar]
  55. Ichii M, Shimazu T, Welner RS, Garrett KP, Zhang Q. 55.  et al. 2010. Functional diversity of stem and progenitor cells with B-lymphopoietic potential. Immunol. Rev. 237:10–21 [Google Scholar]
  56. Allman D, Sambandam A, Kim S, Miller JP, Pagan A. 56.  et al. 2003. Thymopoiesis independent of common lymphoid progenitors. Nat. Immunol. 4:168–74 [Google Scholar]
  57. Welner RS, Pelayo R, Nagai Y, Garrett KP, Wuest TR. 57.  et al. 2008. Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection. Blood 112:3753–61 [Google Scholar]
  58. Lai AY, Watanabe A, O'Brien T, Kondo M. 58.  2009. Pertussis toxin-sensitive G proteins regulate lymphoid lineage specification in multipotent hematopoietic progenitors. Blood 113:5757–64 [Google Scholar]
  59. Kondo M, Scherer DC, Miyamoto T, King AG, Akashi K. 59.  et al. 2000. Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature 407:383–86 [Google Scholar]
  60. Hsu CL, Kikuchi K, Kondo M. 60.  2007. Activation of MEK/ERK signaling pathway is involved in the myeloid lineage commitment. Blood 110:1420–28 [Google Scholar]
  61. Heinzel K, Benz C, Martins VC, Haidl ID, Bleul CC. 61.  2007. Bone marrow-derived hemopoietic precursors commit to the T cell lineage only after arrival in the thymic microenvironment. J. Immunol. 178:858–68 [Google Scholar]
  62. Krueger A, von Boehmer H. 62.  2007. Identification of a T lineage-committed progenitor in adult blood. Immunity 26:105–16 [Google Scholar]
  63. Schwarz BA, Sambandam A, Maillard I, Harman BC, Love PE, Bhandoola A. 63.  2007. Selective thymus settling regulated by cytokine and chemokine receptors. J. Immunol. 178:2008–17 [Google Scholar]
  64. Benz C, Bleul CC. 64.  2005. A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision. J. Exp. Med. 202:21–31 [Google Scholar]
  65. Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV. 65.  2012. Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity. Cell 149:467–82 [Google Scholar]
  66. Heinz S, Benner C, Spann N, Bertolino E, Lin YC. 66.  et al. 2010. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38:576–89 [Google Scholar]
  67. Yu Y, Wang J, Khaled W, Burke S, Li P. 67.  et al. 2012. Bcl11a is essential for lymphoid development and negatively regulates p53. J. Exp. Med. 209:2467–83 [Google Scholar]
  68. Mercer EM, Lin YC, Benner C, Jhunjhunwala S, Dutkowski J. 68.  et al. 2011. Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors. Immunity 35:413–25 [Google Scholar]
  69. De Pooter RF, Kee BL. 69.  2010. E proteins and the regulation of early lymphocyte development. Immunol. Rev. 238:93–109 [Google Scholar]
  70. Semerad CL, Mercer EM, Inlay MA, Weissman IL, Murre C. 70.  2009. E2A proteins maintain the hematopoietic stem cell pool and promote the maturation of myelolymphoid and myeloerythroid progenitors. Proc. Natl. Acad. Sci. USA 106:1930–35 [Google Scholar]
  71. Dias S, Månsson R, Gurbuxani S, Sigvardsson M, Kee BL. 71.  2008. E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity 29:217–27 [Google Scholar]
  72. Winandy S, Wu P, Georgopoulos K. 72.  1995. A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphoma. Cell 83:289–99 [Google Scholar]
  73. Liu P, Keller JR, Ortiz M, Tessarollo L, Rachel RA. 73.  et al. 2003. Bcl11a is essential for normal lymphoid development. Nat. Immunol. 4:525–32 [Google Scholar]
  74. Bain B, Engel I, Robanus Maandag EC, te Riele HP, Voland JR. 74.  et al. 1997. E2A deficiency leads to abnormalities in αβ T-cell development and to rapid development of T-cell lymphomas. Mol. Cell. Biol. 17:4782–91 [Google Scholar]
  75. Györy I, Boller S, Nechanitzky R, Mandel E, Pott S. 75.  et al. 2012. Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells. Genes Dev. 26:668–82 [Google Scholar]
  76. Fahl SP, Crittenden RB, Allman D, Bender TP. 76.  2009. c-Myb is required for pro-B cell differentiation. J. Immunol. 183:5582–92 [Google Scholar]
  77. Greig KT, Carotta S, Nutt SL. 77.  2008. Critical roles for c-Myb in hematopoietic progenitor cells. Semin. Immunol. 20:247–56 [Google Scholar]
  78. Lieu YK, Kumar A, Pajerowski AG, Rogers TJ, Reddy EP. 78.  2004. Requirement of c-myb in T cell development and in mature T cell function. Proc. Natl. Acad. Sci. USA 101:14853–58 [Google Scholar]
  79. Bender TP, Kremer CS, Kraus M, Buch T, Rajewsky K. 79.  2004. Critical functions for c-Myb at three checkpoints during thymocyte development. Nat. Immunol. 5:721–29 [Google Scholar]
  80. Zohren F, Souroullas GP, Luo M, Gerdemann U, Imperato MR. 80.  et al. 2012. The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors. Nat. Immunol. 13:761–69 [Google Scholar]
  81. Li H, Ji M, Klarmann KD, Keller JR. 81.  2010. Repression of Id2 expression by Gfi-1 is required for B-cell and myeloid development. Blood 116:1060–69 [Google Scholar]
  82. Spooner CJ, Cheng JX, Pujadas E, Laslo P, Singh H. 82.  2009. A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates. Immunity 31:576–86 [Google Scholar]
  83. Hock H, Orkin SH. 83.  2006. Zinc-finger transcription factor Gfi-1: versatile regulator of lymphocytes, neutrophils and hematopoietic stem cells. Curr. Opin. Hematol. 13:1–6 [Google Scholar]
  84. Möröy T. 84.  2005. The zinc finger transcription factor Growth factor independence 1 (Gfi1). Int. J. Biochem. Cell Biol. 37:541–46 [Google Scholar]
  85. Yücel R, Karsunky H, Klein-Hitpass L, Möröy T. 85.  2003. The transcriptional repressor Gfi1 affects development of early, uncommitted c-Kit+ T cell progenitors and CD4/CD8 lineage decision in the thymus. J. Exp. Med. 197:831–44 [Google Scholar]
  86. Malin S, McManus S, Busslinger M. 86.  2010. STAT5 in B cell development and leukemia. Curr. Opin. Immunol. 22:168–76 [Google Scholar]
  87. Yao Z, Cui Y, Watford WT, Bream JH, Yamaoka K. 87.  et al. 2006. Stat5a/b are essential for normal lymphoid development and differentiation. Proc. Natl. Acad. Sci. USA 103:1000–5 [Google Scholar]
  88. Seo W, Ikawa T, Kawamoto H, Taniuchi I. 88.  2012. Runx1-Cbfβ facilitates early B lymphocyte development by regulating expression of Ebf1. J. Exp. Med. 209:1255–62 [Google Scholar]
  89. Lukin K, Fields S, Lopez D, Cherrier M, Ternyak K. 89.  et al. 2010. Compound haploinsufficiencies of Ebf1 and Runx1 genes impede B cell lineage progression. Proc. Natl. Acad. Sci. USA 107:7869–74 [Google Scholar]
  90. Guo Y, Maillard I, Chakraborti S, Rothenberg EV, Speck NA. 90.  2008. Core binding factors are necessary for natural killer cell development, and cooperate with Notch signaling during T cell specification. Blood 112:480–92 [Google Scholar]
  91. Talebian L, Li Z, Guo Y, Gaudet J, Speck ME. 91.  et al. 2007. T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage. Blood 109:11–21 [Google Scholar]
  92. Growney JD, Shigematsu H, Li Z, Lee BH, Adelsperger J. 92.  et al. 2005. Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood 106:494–504 [Google Scholar]
  93. Gwin KA, Shapiro MB, Dolence JJ, Huang ZL, Medina KL. 93.  2013. Hoxa9 and flt3 signaling synergistically regulate an early checkpoint in lymphopoiesis. J. Immunol. 191:745–54 [Google Scholar]
  94. Kosan C, Saba I, Godmann M, Herold S, Herkert B. 94.  et al. 2010. Transcription factor Miz-1 is required to regulate interleukin-7 receptor signaling at early commitment stages of B cell differentiation. Immunity 33:917–28 [Google Scholar]
  95. Saba I, Kosan C, Vassen L, Möröy T. 95.  2011. IL-7R-dependent survival and differentiation of early T-lineage progenitors is regulated by the BTB/POZ domain transcription factor Miz-1. Blood 117:3370–81 [Google Scholar]
  96. Igarashi H, Gregory SC, Yokota T, Sakaguchi N, Kincade PW. 96.  2002. Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity 17:117–30 [Google Scholar]
  97. Kondo M, Weissman IL, Akashi K. 97.  1997. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661–72 [Google Scholar]
  98. Pereira de Sousa A, Berthault C, Granato A, Dias S, Ramond C. 98.  et al. 2012. Inhibitors of DNA binding proteins restrict T cell potential by repressing Notch1 expression in Flt3-negative common lymphoid progenitors. J. Immunol. 189:3822–30 [Google Scholar]
  99. Inlay MA, Bhattacharya D, Sahoo D, Serwold T, Seita J. 99.  et al. 2009. Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development. Genes Dev. 23:2376–81 [Google Scholar]
  100. Karsunky H, Inlay MA, Serwold T, Bhattacharya D, Weissman IL. 100.  2008. Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages. Blood 111:5562–70 [Google Scholar]
  101. Holmes ML, Carotta S, Corcoran LM, Nutt SL. 101.  2006. Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment. Genes Dev. 20:933–38 [Google Scholar]
  102. Zandi S, Åhsberg J, Tsapogas P, Stjernberg J, Qian H, Sigvardsson M. 102.  2012. Single-cell analysis of early B-lymphocyte development suggests independent regulation of lineage specification and commitment in vivo. Proc. Natl. Acad. Sci. USA 109:15871–76 [Google Scholar]
  103. Mansson R, Zandi S, Anderson K, Martensson IL, Jacobsen SE. 103.  et al. 2008. B-lineage commitment prior to surface expression of B220 and CD19 on hematopoietic progenitor cells. Blood 112:1048–55 [Google Scholar]
  104. Feyerabend TB, Terszowski G, Tietz A, Blum C, Luche H. 104.  et al. 2009. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity 30:67–79 [Google Scholar]
  105. Weerkamp F, Baert MR, Brugman MH, Dik WA, de Haas EF. 105.  et al. 2006. Human thymus contains multipotent progenitors with T/B lymphoid, myeloid, and erythroid lineage potential. Blood 107:3131–37 [Google Scholar]
  106. De Smedt M, Hoebeke I, Reynvoet K, Leclercq G, Plum J. 106.  2005. Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. Blood 106:3498–506 [Google Scholar]
  107. Sambandam A, Maillard I, Zediak VP, Xu L, Gerstein RM. 107.  et al. 2005. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat. Immunol. 6:663–70 [Google Scholar]
  108. Tan JB, Visan I, Yuan JS, Guidos CJ. 108.  2005. Requirement for Notch1 signals at sequential early stages of intrathymic T cell development. Nat. Immunol. 6:671–79 [Google Scholar]
  109. Harman BC, Jenkinson WE, Parnell SM, Rossi SW, Jenkinson EJ, Anderson G. 109.  2005. T/B lineage choice occurs prior to intrathymic Notch signalling. Blood 106:886–92 [Google Scholar]
  110. Masuda K, Itoi M, Amagai T, Minato N, Katsura Y, Kawamoto H. 110.  2005. Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell lineages. J. Immunol. 174:2525–32 [Google Scholar]
  111. Yui MA, Feng N, Rothenberg EV. 111.  2010. Fine-scale staging of T cell lineage commitment in adult mouse thymus. J. Immunol. 185:284–93 [Google Scholar]
  112. Bell JJ, Bhandoola A. 112.  2008. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 452:764–67 [Google Scholar]
  113. Wada H, Masuda K, Satoh R, Kakugawa K, Ikawa T. 113.  et al. 2008. Adult T-cell progenitors retain myeloid potential. Nature 452:768–72 [Google Scholar]
  114. Taghon T, Yui MA, Rothenberg EV. 114.  2007. Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3. Nat. Immunol. 8:845–55 [Google Scholar]
  115. Balciunaite G, Ceredig R, Rolink AG. 115.  2005. The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential. Blood 105:1930–36 [Google Scholar]
  116. Lu M, Tayu R, Ikawa T, Masuda K, Matsumoto I. 116.  et al. 2005. The earliest thymic progenitors in adults are restricted to T, NK, and dendritic cell lineage and have a potential to form more diverse TCRβ chains than fetal progenitors. J. Immunol. 175:5848–56 [Google Scholar]
  117. Shen HQ, Lu M, Ikawa T, Masuda K, Ohmura K. 117.  et al. 2003. T/NK bipotent progenitors in the thymus retain the potential to generate dendritic cells. J. Immunol. 171:3401–6 [Google Scholar]
  118. Ikawa T, Fujimoto S, Kawamoto H, Katsura Y, Yokota Y. 118.  2001. Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc. Natl. Acad. Sci. USA 98:5164–69 [Google Scholar]
  119. Michie AM, Carlyle JR, Schmitt TM, Ljutic B, Cho SK. 119.  et al. 2000. Clonal characterization of a bipotent T cell and NK cell progenitor in the mouse fetal thymus. J. Immunol. 164:1730–33 [Google Scholar]
  120. Wu L, Li CL, Shortman K. 120.  1996. Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny. J. Exp. Med. 184:903–11 [Google Scholar]
  121. Rothenberg EV. 121.  2011. T cell lineage commitment: identity and renunciation. J. Immunol. 186:6649–55 [Google Scholar]
  122. Welinder E, Åhsberg J, Sigvardsson M. 122.  2011. B-lymphocyte commitment: identifying the point of no return. Semin. Immunol. 23:335–40 [Google Scholar]
  123. Malin S, McManus S, Cobaleda C, Novatchkova M, Delogu A. 123.  et al. 2010. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat. Immunol. 11:171–79 [Google Scholar]
  124. Lin YC, Jhunjhunwala S, Benner C, Heinz S, Welinder E. 124.  et al. 2010. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat. Immunol. 11:635–43 [Google Scholar]
  125. Jones ME, Zhuang Y. 125.  2009. Regulation of V(D)J recombination by E-protein transcription factors. Adv. Exp. Med. Biol. 650:148–56 [Google Scholar]
  126. Hsu LY, Lauring J, Liang HE, Greenbaum S, Cado D. 126.  et al. 2003. A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity 19:105–17 [Google Scholar]
  127. Kee BL. 127.  2009. E and ID proteins branch out. Nat. Rev. Immunol. 9:175–84 [Google Scholar]
  128. Mansson R, Welinder E, Åhsberg J, Lin YC, Benner C. 128.  et al. 2012. Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate. Proc. Natl. Acad. Sci. USA 109:21028–33 [Google Scholar]
  129. Welinder E, Mansson R, Mercer EM, Bryder D, Sigvardsson M, Murre C. 129.  2011. The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor. Proc. Natl. Acad. Sci. USA 108:17402–7 [Google Scholar]
  130. O'Riordan M, Grosschedl R. 130.  1999. Coordinate regulation of B cell differentiation by the transcription factors EBF and E2A. Immunity 11:21–31 [Google Scholar]
  131. Sigvardsson M, O'Riordan M, Grosschedl R. 131.  1997. EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity 7:25–36 [Google Scholar]
  132. Decker T, Pasca di Magliano M, McManus S, Sun Q, Bonifer C. 132.  et al. 2009. Stepwise activation of enhancer and promoter regions of the B cell commitment gene Pax5 in early lymphopoiesis. Immunity 30:508–20 [Google Scholar]
  133. Ferreiros-Vidal I, Carroll T, Taylor B, Terry A, Liang Z. 133.  et al. 2013. Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation. Blood 121:1769–82 [Google Scholar]
  134. Reynaud D, Demarco IA, Reddy KL, Schjerven H, Bertolino E. 134.  et al. 2008. Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros. Nat. Immunol. 9:927–36 [Google Scholar]
  135. Wang JH, Nichogiannopoulou A, Wu L, Sun L, Sharpe AH. 135.  et al. 1996. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 5:537–49 [Google Scholar]
  136. Kirstetter P, Thomas M, Dierich A, Kastner P, Chan S. 136.  2002. Ikaros is critical for B cell differentiation and function. Eur. J. Immunol. 32:720–30 [Google Scholar]
  137. Lee BS, Dekker JD, Lee BK, Iyer VR, Sleckman BP. 137.  et al. 2013. The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination. Mol. Cell. Biol. 33:1768–81 [Google Scholar]
  138. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC. 138.  et al. 2007. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131:146–59 [Google Scholar]
  139. Hsu CL, King-Fleischman AG, Lai AY, Matsumoto Y, Weissman IL, Kondo M. 139.  2006. Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors. Proc. Natl. Acad. Sci. USA 103:672–77 [Google Scholar]
  140. Bussmann LH, Schubert A, Vu Manh TP, De Andres L, Desbordes SC. 140.  et al. 2009. A robust and highly efficient immune cell reprogramming system. Cell Stem Cell 5:554–66 [Google Scholar]
  141. Xie H, Ye M, Feng R, Graf T. 141.  2004. Stepwise reprogramming of B cells into macrophages. Cell 117:663–76 [Google Scholar]
  142. Iwasaki-Arai J, Iwasaki H, Miyamoto T, Watanabe S, Akashi K. 142.  2003. Enforced Granulocyte/Macrophage Colony-Stimulating Factor signals do not support lymphopoiesis, but instruct lymphoid to myelomonocytic lineage conversion. J. Exp. Med. 197:1311–22 [Google Scholar]
  143. Kondo M, Scherer DC, Miyamoto T, King AG, Akashi K. 143.  et al. 2000. Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature 407:383–86 [Google Scholar]
  144. Leeanansaksiri W, Wang H, Gooya JM, Renn K, Abshari M. 144.  et al. 2005. IL-3 induces inhibitor of DNA-binding protein-1 in hemopoietic progenitor cells and promotes myeloid cell development. J. Immunol. 174:7014–21 [Google Scholar]
  145. Ikawa T, Kawamoto H, Goldrath AW, Murre C. 145.  2006. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J. Exp. Med. 203:1329–42 [Google Scholar]
  146. Zarnegar MA, Rothenberg EV. 146.  2012. Ikaros represses and activates PU.1 cell-type-specifically through the multifunctional Sfpi1 URE and a myeloid specific enhancer. Oncogene 31:4647–54 [Google Scholar]
  147. Tsapogas P, Zandi S, Ahsberg J, Zetterblad J, Welinder E. 147.  et al. 2011. IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors. Blood 118:1283–90 [Google Scholar]
  148. Kikuchi K, Kasai H, Watanabe A, Lai AY, Kondo M. 148.  2008. IL-7 specifies B cell fate at the common lymphoid progenitor to pre-proB transition stage by maintaining early B cell factor expression. J. Immunol. 181:383–92 [Google Scholar]
  149. Ochiai K, Maienschein-Cline M, Mandal M, Triggs JR, Bertolino E. 149.  et al. 2012. A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation. Nat. Immunol. 13:300–7 [Google Scholar]
  150. Dengler HS, Baracho GV, Omori SA, Bruckner S, Arden KC. 150.  et al. 2008. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nat. Immunol. 9:1388–98 [Google Scholar]
  151. Amin RH, Schlissel MS. 151.  2008. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat. Immunol. 9:613–22 [Google Scholar]
  152. Johnson SE, Shah N, Bajer AA, LeBien TW. 152.  2008. IL-7 activates the phosphatidylinositol 3-kinase/AKT pathway in normal human thymocytes but not normal human B cell precursors. J. Immunol. 180:8109–17 [Google Scholar]
  153. Johnson K, Chaumeil J, Micsinai M, Wang JM, Ramsey LB. 153.  et al. 2012. IL-7 functionally segregates the pro-B cell stage by regulating transcription of recombination mediators across cell cycle. J. Immunol. 188:6084–92 [Google Scholar]
  154. Herzog S, Hug E, Meixlsperger S, Paik JH, DePinho RA. 154.  et al. 2008. SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. Nat. Immunol. 9:623–31 [Google Scholar]
  155. McManus S, Ebert A, Salvagiotto G, Medvedovic J, Sun Q. 155.  et al. 2011. The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells. EMBO J. 30:2388–404 [Google Scholar]
  156. Mansson R, Zandi S, Welinder E, Tsapogas P, Sakaguchi N. 156.  et al. 2010. Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity. Blood 115:2601–9 [Google Scholar]
  157. Treiber T, Mandel EM, Pott S, Gyory I, Firner S. 157.  et al. 2010. Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription-independent poising of chromatin. Immunity 32:714–25 [Google Scholar]
  158. Roessler S, Gyory I, Imhof S, Spivakov M, Williams RR. 158.  et al. 2007. Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5. Mol. Cell. Biol. 27:579–94 [Google Scholar]
  159. Pongubala JM, Northrup DL, Lancki DW, Medina KL, Treiber T. 159.  et al. 2008. Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nat. Immunol. 9:203–15 [Google Scholar]
  160. Maier H, Ostraat R, Gao H, Fields S, Shinton SA. 160.  et al. 2004. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat. Immunol. 5:1069–77 [Google Scholar]
  161. Schebesta A, McManus S, Salvagiotto G, Delogu A, Busslinger GA, Busslinger M. 161.  2007. Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity 27:49–63 [Google Scholar]
  162. Thal MA, Carvalho TL, He T, Kim HG, Gao H. 162.  et al. 2009. Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage. Proc. Natl. Acad. Sci. USA 106:552–57 [Google Scholar]
  163. Bhalla S, Spaulding C, Brumbaugh RL, Zagort DE, Massari ME. 163.  et al. 2008. Differential roles for the E2A activation domains in B lymphocytes and macrophages. J. Immunol. 180:1694–703 [Google Scholar]
  164. Revilla-i-Domingo R, Bilic I, Vilagos B, Tagoh H, Ebert A. 164.  et al. 2012. The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis. EMBO J. 31:3130–46 [Google Scholar]
  165. Capron C, Lecluse Y, Kaushik AL, Foudi A, Lacout C. 165.  et al. 2006. The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation. Blood 107:4678–86 [Google Scholar]
  166. Painter MW, Davis S, Hardy RR, Mathis D, Benoist C. 166.  2011. Transcriptomes of the B and T lineages compared by multiplatform microarray profiling. J. Immunol. 186:3047–57 [Google Scholar]
  167. Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F. 167.  et al. 2010. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 32:317–28 [Google Scholar]
  168. Yashiro-Ohtani Y, Ohtani T, Pear WS. 168.  2010. Notch regulation of early thymocyte development. Semin. Immunol. 22:261–69 [Google Scholar]
  169. Weber BN, Chi AW, Chavez A, Yashiro-Ohtani Y, Yang Q. 169.  et al. 2011. A critical role for TCF-1 in T-lineage specification and differentiation. Nature 476:63–68 [Google Scholar]
  170. Germar K, Dose M, Konstantinou T, Zhang J, Wang H. 170.  et al. 2011. T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc. Natl. Acad. Sci. USA 108:20060–65 [Google Scholar]
  171. Okamura RM, Sigvardsson M, Galceran J, Verbeek S, Clevers H, Grosschedl R. 171.  1998. Redundant regulation of T cell differentiation and TCRβ gene expression by the transcription factors LEF-1 and TCF-1. Immunity 8:11–20 [Google Scholar]
  172. Verbeek S, Izon D, Hofhuis F, Robanus-Maandag E, te Riele H. 172.  et al. 1995. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374:70–74 [Google Scholar]
  173. Hosoya T, Maillard I, Engel JD. 173.  2010. From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation. Immunol. Rev. 238:110–25 [Google Scholar]
  174. Ho IC, Tai TS, Pai SY. 174.  2009. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat. Rev. Immunol. 9:125–35 [Google Scholar]
  175. Hozumi K, Negishi N, Tsuchiya I, Abe N, Hirano K. 175.  et al. 2008. Notch signaling is necessary for GATA3 function in the initiation of T cell development. Eur. J. Immunol. 38:977–85 [Google Scholar]
  176. Hattori N, Kawamoto H, Fujimoto S, Kuno K, Katsura Y. 176.  1996. Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus. J. Exp. Med. 184:1137–47 [Google Scholar]
  177. Ting CN, Olson MC, Barton KP, Leiden JM. 177.  1996. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384:474–78 [Google Scholar]
  178. Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R. 178.  et al. 2010. An essential developmental checkpoint for production of the T cell lineage. Science 329:93–96 [Google Scholar]
  179. Li L, Leid M, Rothenberg EV. 179.  2010. An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. Science 329:89–93 [Google Scholar]
  180. Li P, Burke S, Wang J, Chen X, Ortiz M. 180.  et al. 2010. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science 329:85–89 [Google Scholar]
  181. Albu DI, Feng D, Bhattacharya D, Jenkins NA, Copeland NG. 181.  et al. 2007. BCL11B is required for positive selection and survival of double-positive thymocytes. J. Exp. Med. 204:3003–15 [Google Scholar]
  182. Tydell CC, David-Fung ES, Moore JE, Rowen L, Taghon T, Rothenberg EV. 182.  2007. Molecular dissection of prethymic progenitor entry into the T lymphocyte developmental pathway. J. Immunol. 179:421–38 [Google Scholar]
  183. Georgescu C, Longabaugh WJ, Scripture-Adams DD, David-Fung ES, Yui MA. 183.  et al. 2008. A gene regulatory network armature for T lymphocyte specification. Proc. Natl. Acad. Sci. USA 105:20100–5 [Google Scholar]
  184. Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J. 184.  et al. 2006. The requirement for Notch signaling at the β-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J. Exp. Med. 203:2239–45 [Google Scholar]
  185. Reizis B, Leder P. 185.  2002. Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway. Genes Dev. 16:295–300 [Google Scholar]
  186. David-Fung ES, Butler R, Buzi G, Yui MA, Diamond RA. 186.  et al. 2009. Transcription factor expression dynamics of early T-lymphocyte specification and commitment. Dev. Biol. 325:444–67 [Google Scholar]
  187. Wang D, Claus CL, Vaccarelli G, Braunstein M, Schmitt TM. 187.  et al. 2006. The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors. J. Immunol. 177:109–19 [Google Scholar]
  188. Anderson MK, Hernandez-Hoyos G, Diamond RA, Rothenberg EV. 188.  1999. Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development 126:3131–48 [Google Scholar]
  189. Doan LL, Porter SD, Duan Z, Flubacher MM, Montoya D. 189.  et al. 2004. Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic Acids Res. 32:2508–19 [Google Scholar]
  190. Franco CB, Scripture-Adams DD, Proekt I, Taghon T, Weiss AH. 190.  et al. 2006. Notch/Delta signaling constrains reengineering of pro-T cells by PU.1. Proc. Natl. Acad. Sci. USA 103:11993–98 [Google Scholar]
  191. Dionne CJ, Tse KY, Weiss AH, Franco CB, Wiest DL. 191.  et al. 2005. Subversion of T lineage commitment by PU.1 in a clonal cell line system. Dev. Biol. 280:448–66 [Google Scholar]
  192. Tiemessen MM, Baert MR, Schonewille T, Brugman MH, Famili F. 192.  et al. 2012. The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas. PLoS Biol. 10:e1001430 [Google Scholar]
  193. Yu S, Zhou X, Steinke FC, Liu C, Chen SC. 193.  et al. 2012. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity 37:813–26 [Google Scholar]
  194. Anderson G, Jenkinson EJ. 194.  2007. Investigating central tolerance with reaggregate thymus organ cultures. Methods Mol. Biol. 380:185–96 [Google Scholar]
  195. Katsura Y, Kawamoto H. 195.  2001. Stepwise lineage restriction of progenitors in lympho-myelopoiesis. Int. Rev. Immunol. 20:1–20 [Google Scholar]
  196. Starr TK, Jameson SC, Hogquist KA. 196.  2003. Positive and negative selection of T cells. Annu. Rev. Immunol. 21:139–76 [Google Scholar]
  197. Schmitt TM, Zúñiga-Pflücker JC. 197.  2002. Induction of T cell development from hematopoietic progenitor cells by Delta-like-1 in vitro. Immunity 17:749–56 [Google Scholar]
  198. Besseyrias V, Fiorini E, Strobl LJ, Zimber-Strobl U, Dumortier A. 198.  et al. 2007. Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation. J. Exp. Med. 204:331–43 [Google Scholar]
  199. Mohtashami M, Shah DK, Nakase H, Kianizad K, Petrie HT, Zúñiga-Pflücker JC. 199.  2010. Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes. J. Immunol. 185:867–76 [Google Scholar]
  200. Sambandam A, Maillard I, Zediak VP, Xu L, Gerstein RM. 200.  et al. 2005. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat. Immunol. 6:663–70 [Google Scholar]
  201. Waskow C, Paul S, Haller C, Gassmann M, Rodewald HR. 201.  2002. Viable c-KitW/W mutants reveal pivotal role for c-kit in the maintenance of lymphopoiesis. Immunity 17:277–88 [Google Scholar]
  202. Massa S, Balciunaite G, Ceredig R, Rolink AG. 202.  2006. Critical role for c-kit (CD117) in T cell lineage commitment and early thymocyte development in vitro. Eur. J. Immunol. 36:526–32 [Google Scholar]
  203. Wang H, Pierce LJ, Spangrude GJ. 203.  2006. Distinct roles of IL-7 and stem cell factor in the OP9-DL1 T-cell differentiation culture system. Exp. Hematol. 34:1730–40 [Google Scholar]
  204. Laiosa CV, Stadtfeld M, Xie H, de Andres-Aguayo L, Graf T. 204.  2006. Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBPα and PU.1 transcription factors. Immunity 25:731–44 [Google Scholar]
  205. Schmitt TM, De Pooter RF, Gronski MA, Cho SK, Ohashi PS, Zúñiga-Pflücker JC. 205.  2004. Induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitro. Nat. Immunol. 5:410–17 [Google Scholar]
  206. Taghon TN, David ES, Zúñiga-Pflücker JC, Rothenberg EV. 206.  2005. Delayed, asynchronous, and reversible T-lineage specification induced by Notch/Delta signaling. Genes Dev. 19:965–78 [Google Scholar]
  207. Ciofani M, Knowles GC, Wiest DL, von Boehmer H, Zúñiga-Pflücker JC. 207.  2006. Stage-specific and differential Notch dependency at the αβ and γδ T lineage bifurcation. Immunity 25:105–16 [Google Scholar]
  208. Feng N, Vegh P, Rothenberg EV, Yui MA. 208.  2011. Lineage divergence at the first TCR-dependent checkpoint: preferential γδ and impaired αβ T cell development in nonobese diabetic mice. J. Immunol. 186:826–37 [Google Scholar]
  209. Huang J, Durum SK, Muegge K. 209.  2001. Cutting edge: histone acetylation and recombination at the TCRγ locus follows IL-7 induction. J. Immunol. 167:6073–77 [Google Scholar]
  210. Ye SK, Agata Y, Lee HC, Kurooka H, Kitamura T. 210.  et al. 2001. The IL-7 receptor controls the accessibility of the TCRγ locus by Stat5 and histone acetylation. Immunity 15:813–23 [Google Scholar]
  211. Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E. 211.  et al. 2012. Transcription factor RORα is critical for nuocyte development. Nat. Immunol. 13:229–36 [Google Scholar]
  212. Manesso E, Chickarmane V, Kueh HY, Rothenberg EV, Peterson C. 212.  2013. Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence. J. R. Soc. Interface 10:20120774 [Google Scholar]
  213. Masuda K, Kakugawa K, Nakayama T, Minato M, Katsura Y, Kawamoto H. 213.  2007. T cell lineage determination precedes the initiation of TCRβ rearrangement. J. Immunol. 179:3699–706 [Google Scholar]
  214. Wu X, Satpathy AT, KC W, Liu P, Murphy TL, Murphy KM. 214.  2013. Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo. PLoS ONE 8:e64800 [Google Scholar]
  215. Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R. 215.  et al. 2013. The transcriptional landscape of αβ T cell differentiation. Nat. Immunol. 14:619–32 [Google Scholar]
  216. Ikawa T, Kawamoto H, Goldrath AW, Murre C. 216.  2006. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J. Exp. Med. 203:1329–42 [Google Scholar]
  217. Miyazaki M, Rivera RR, Miyazaki K, Lin YC, Agata Y, Murre C. 217.  2011. The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells. Nat. Immunol. 12:992–1001 [Google Scholar]
  218. Wojciechowski J, Lai A, Kondo M, Zhuang Y. 218.  2007. E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J. Immunol. 178:5717–26 [Google Scholar]
  219. Hollenhorst PC, Shah AA, Hopkins C, Graves BJ. 219.  2007. Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family. Genes Dev. 21:1882–94 [Google Scholar]
  220. Laiosa CV, Stadtfeld M, Graf T. 220.  2006. Determinants of lymphoid-myeloid lineage diversification. Annu. Rev. Immunol. 24:705–38 [Google Scholar]
  221. Lefebvre JM, Haks MC, Carleton MO, Rhodes M, Sinnathamby G. 221.  et al. 2005. Enforced expression of Spi-B reverses T lineage commitment and blocks β-selection. J. Immunol. 174:6184–94 [Google Scholar]
  222. Anderson MK, Weiss AH, Hernandez-Hoyos G, Dionne CJ, Rothenberg EV. 222.  2002. Constitutive expression of PU.1 in fetal hematopoietic progenitors blocks T cell development at the pro-T cell stage. Immunity 16:285–96 [Google Scholar]
  223. Zarnegar MA, Chen J, Rothenberg EV. 223.  2010. Cell-type-specific activation and repression of PU.1 by a complex of discrete, functionally specialized cis-regulatory elements. Mol. Cell. Biol. 30:4922–39 [Google Scholar]
  224. Huang G, Zhang P, Hirai H, Elf S, Yan X. 224.  et al. 2008. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat. Genet. 40:51–60 [Google Scholar]
  225. Dontje W, Schotte R, Cupedo T, Nagasawa M, Scheeren F. 225.  et al. 2006. Delta-Like1-induced Notch1 signalling regulates the human plasmacytoid dendritic cell versus T cell lineage decision through control of GATA-3 and Spi-B. Blood 107:2446–52 [Google Scholar]
  226. Del Real MM, Rothenberg EV. 226.  2013. Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and Gata3. Development 140:1207–19 [Google Scholar]
  227. Schmitt TM, Ciofani M, Petrie HT, Zúñiga-Pflücker JC. 227.  2004. Maintenance of T cell specification and differentiation requires recurrent Notch receptor-ligand interactions. J. Exp. Med. 200:469–79 [Google Scholar]
  228. Li HS, Yang CY, Nallaparaju KC, Zhang H, Liu YJ. 228.  et al. 2012. The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development. Blood 120:4363–73 [Google Scholar]
  229. Ramirez K, Chandler KJ, Spaulding C, Zandi S, Sigvardsson M. 229.  et al. 2012. Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1. Immunity 36:921–32 [Google Scholar]
  230. Cohen NR, Brennan PJ, Shay T, Watts GF, Brigl M. 230.  et al. 2013. Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat. Immunol. 14:90–99 [Google Scholar]
  231. Gascoyne DM, Long E, Veiga-Fernandes H, de Boer J, Williams O. 231.  et al. 2009. The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development. Nat. Immunol. 10:1118–24 [Google Scholar]
  232. Kamizono S, Duncan GS, Seidel MG, Morimoto A, Hamada K. 232.  et al. 2009. Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. J. Exp. Med. 206:2977–86 [Google Scholar]
  233. Kastner P, Chan S, Vogel WK, Zhang LJ, Topark-Ngarm A. 233.  et al. 2010. Bcl11b represses a mature T-cell gene expression program in immature CD4+CD8+ thymocytes. Eur. J. Immunol. 40:2143–54 [Google Scholar]
  234. García-Ojeda ME, Klein Wolterink RG, Lemaître F, Richard-Le Goff O, Hasan M. 234.  et al. 2013. GATA-3 promotes T cell specification by repressing B cell potential in pro-T cells. Blood 121:1749–59 [Google Scholar]
  235. Ciofani M, Zúñiga-Pflücker JC. 235.  2005. Notch promotes survival of pre-T cells at the β-selection checkpoint by regulating cellular metabolism. Nat. Immunol. 6:881–88 [Google Scholar]
  236. Hosoya T, Kuroha T, Moriguchi T, Cummings D, Maillard I. 236.  et al. 2009. GATA-3 is required for early T lineage progenitor development. J. Exp. Med. 206:2987–3000 [Google Scholar]
  237. Jones ME, Zhuang Y. 237.  2011. Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development. Immunol. Res. 49:202–15 [Google Scholar]
  238. Jones ME, Zhuang Y. 238.  2007. Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors. Immunity 27:860–70 [Google Scholar]
  239. Schwartz R, Engel I, Fallahi-Sichani M, Petrie HT, Murre C. 239.  2006. Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development. Proc. Natl. Acad. Sci. USA 103:9976–81 [Google Scholar]
  240. Barndt RJ, Dai M, Zhuang Y. 240.  2000. Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB. Mol. Cell. Biol. 20:6677–85 [Google Scholar]
  241. Engel I, Johns C, Bain G, Rivera RR, Murre C. 241.  2001. Early thymocyte development is regulated by modulation of E2A protein activity. J. Exp. Med. 194:733–46 [Google Scholar]
  242. Xu W, Carr T, Ramirez K, McGregor S, Sigvardsson M, Kee BL. 242.  2013. E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment. Blood 121:1534–42 [Google Scholar]
  243. Braunstein M, Anderson MK. 243.  2012. HEB in the spotlight: transcriptional regulation of T-cell specification, commitment, and developmental plasticity. Clin. Dev. Immunol. 2012:678705 [Google Scholar]
  244. Yashiro-Ohtani Y, He Y, Ohtani T, Jones ME, Shestova O. 244.  et al. 2009. Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A. Genes Dev. 23:1665–76 [Google Scholar]
  245. Taghon T, Yui MA, Pant R, Diamond RA, Rothenberg EV. 245.  2006. Developmental and molecular characterization of emerging β- and γδ-selected pre-T cells in the adult mouse thymus. Immunity 24:53–64 [Google Scholar]
  246. Lauritsen JP, Wong GW, Lee SY, Lefebvre JM, Ciofani M. 246.  et al. 2009. Marked induction of the helix-loop-helix protein Id3 promotes the γδ T cell fate and renders their functional maturation Notch independent. Immunity 31:565–75 [Google Scholar]
  247. Bain G, Cravatt CB, Loomans C, Alberola-Ila J, Hedrick SM, Murre C. 247.  2001. Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nat. Immunol. 2:165–71 [Google Scholar]
  248. Masson F, Minnich M, Olshansky M, Bilic I, Mount AM. 248.  et al. 2013. Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation. J. Immunol. 190:4585–94 [Google Scholar]
  249. Rothenberg EV, Champhekar A, Damle S, Del Real MM, Kueh HY. 249.  et al. 2013. Transcriptional establishment of cell-type identity: Dynamics and causal mechanisms of T-cell lineage commitment. Cold Spring Harb. Symp. Quant. Biol. In press. doi: 10.1101/sqb.2013.78.020271
  250. Anderson MK, Hernandez-Hoyos G, Dionne CJ, Arias AM, Chen D, Rothenberg EV. 250.  2002. Definition of regulatory network elements for T cell development by perturbation analysis with PU.1 and GATA-3. Dev. Biol. 246:103–21 [Google Scholar]
  251. Li L, Dose M, Kueh HY, Mosadeghi R, Gounari F, Rothenberg EV. 251.  2013. A far downstream enhancer for murine Bcl11b controls its T-cell specific expression. Blood 122:902–11 [Google Scholar]
  252. Kwon K, Hutter C, Sun Q, Bilic I, Cobaleda C. 252.  et al. 2008. Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development. Immunity 28:751–62 [Google Scholar]
  253. Seet CS, Brumbaugh RL, Kee BL. 253.  2004. Early B Cell Factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J. Exp. Med. 199:1689–700 [Google Scholar]
  254. Yashiro-Ohtani Y, He Y, Ohtani T, Jones ME, Shestova O. 254.  et al. 2009. Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A. Genes Dev. 23:1665–76 [Google Scholar]
  255. Koltsova EK, Ciofani M, Benezra R, Miyazaki T, Clipstone N. 255.  et al. 2007. Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the β-selection checkpoint. J. Immunol. 179:4694–703 [Google Scholar]
  256. Kaech SM, Cui W. 256.  2012. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat. Rev. Immunol. 12:749–61 [Google Scholar]
  257. Nutt SL, Heavey B, Rolink AG, Busslinger M. 257.  1999. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401:556–62 [Google Scholar]
  258. Rolink AG, Nutt SL, Melchers F, Busslinger M. 258.  1999. Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature 401:603–6 [Google Scholar]
  259. Souabni A, Cobaleda C, Schebesta M, Busslinger M. 259.  2002. Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Immunity 17:781–93 [Google Scholar]
  260. Cotta CV, Zhang Z, Kim HG, Klug CA. 260.  2003. Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development. Blood 101:4342–46 [Google Scholar]
  261. Banerjee A, Northrup D, Boukarabila H, Jacobsen SE, Allman D. 261.  2013. Transcriptional repression of Gata3 is essential for early B cell commitment. Immunity 38:930–42 [Google Scholar]
  262. Nechanitzky R, Akbas D, Scherer S, Györy I, Hoyler T. 262.  et al. 2013. Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells. Nat. Immunol. 14:867–75 [Google Scholar]
  263. Goetz CA, Harmon IR, O'Neil JJ, Burchill MA, Johanns TM, Farrar MA. 263.  2005. Restricted STAT5 activation dictates appropriate thymic B versus T cell lineage commitment. J. Immunol. 174:7753–63 [Google Scholar]
  264. Massa S, Balciunaite G, Ceredig R, Rolink AG. 264.  2006. Critical role for c-kit (CD117) in T cell lineage commitment and early thymocyte development in vitro. Eur. J. Immunol. 36:526–32 [Google Scholar]
  265. Moller C, Alfredsson J, Engstrom M, Wootz H, Xiang Z. 265.  et al. 2005. Stem cell factor promotes mast cell survival via inactivation of FOXO3a-mediated transcriptional induction and MEK-regulated phosphorylation of the proapoptotic protein Bim. Blood 106:1330–36 [Google Scholar]
  266. Nie L, Xu M, Vladimirova A, Sun XH. 266.  2003. Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities. EMBO J. 22:5780–92 [Google Scholar]
  267. Cherrier M, Sawa S, Eberl G. 267.  2012. Notch, Id2, and RORγt sequentially orchestrate the fetal development of lymphoid tissue inducer cells. J. Exp. Med. 209:729–40 [Google Scholar]
  268. Boos MD, Yokota Y, Eberl G, Kee BL. 268.  2007. Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J. Exp. Med. 204:1119–30 [Google Scholar]
  269. Nie L, Perry SS, Zhao Y, Huang J, Kincade PW. 269.  et al. 2008. Regulation of lymphocyte development by cell-type-specific interpretation of Notch signals. Mol. Cell. Biol. 28:2078–90 [Google Scholar]
  270. Weishaupt H, Sigvardsson M, Attema JL. 270.  2010. Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells. Blood 115:247–56 [Google Scholar]
  271. Wendorff AA, Koch U, Wunderlich FT, Wirth S, Dubey C. 271.  et al. 2010. Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation. Immunity 33:671–84 [Google Scholar]
  272. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP. 272.  et al. 2013. Innate lymphoid cells—a proposal for uniform nomenclature. Nat. Rev. Immunol. 13:145–49 [Google Scholar]
  273. Rankin L, Groom J, Mielke LA, Seillet C, Belz GT. 273.  2013. Diversity, function, and transcriptional regulation of gut innate lymphocytes. Front. Immunol. 4:22 [Google Scholar]
  274. Yang Q, Monticelli LA, Saenz SA, Chi AW, Sonnenberg GF. 274.  et al. 2013. T cell factor 1 is required for group 2 innate lymphoid cell generation. Immunity 38:694–704 [Google Scholar]
  275. Hoyler T, Klose CS, Souabni A, Turqueti-Neves A, Pfeifer D. 275.  et al. 2012. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37:634–48 [Google Scholar]
  276. Mjösberg J, Bernink J, Peters C, Spits H. 276.  2012. Transcriptional control of innate lymphoid cells. Eur. J. Immunol. 42:1916–23 [Google Scholar]
/content/journals/10.1146/annurev-immunol-032712-100024
Loading
/content/journals/10.1146/annurev-immunol-032712-100024
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error