1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genomics and Human Genetics
  4. Volume 21, 2020
  5. Article

Annual Review of Genomics and Human Genetics

Volume 21, 2020

Cell Lineage Tracing and Cellular Diversity in Humans

Abstract

Tracing cell lineages is fundamental for understanding the rules governing development in multicellular organisms and delineating complex biological processes involving the differentiation of multiple cell types with distinct lineage hierarchies. In humans, experimental lineage tracing is unethical, and one has to rely on natural-mutation markers that are created within cells as they proliferate and age. Recent studies have demonstrated that it is now possible to trace lineages in normal, noncancerous cells with a variety of data types using natural variations in the nuclear and mitochondrial DNA as well as variations in DNA methylation status. It is also apparent that the scientific community is on the verge of being able to make a comprehensive and detailed cell lineage map of human embryonic and fetal development. In this review, we discuss the advantages and disadvantages of different approaches and markers for lineage tracing. We also describe the general conceptual design for how to derive a lineage map for humans.

Keyword(s): development, genome, methylation, mitochondria, nuclear, variant
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-083118-015241
2020-08-31
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/genom/21/1/annurev-genom-083118-015241.html?itemId=/content/journals/10.1146/annurev-genom-083118-015241&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    1000 Genomes Proj. Consort 2015. A global reference for human genetic variation. Nature 526:68–74
     [Google Scholar]
  2. 2. 
    Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS et al. 2012. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492:438–42
     [Google Scholar]
  3. 3. 
    Abyzov A, Tomasini L, Zhou B, Vasmatzis N, Coppola G et al. 2017. One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin. Genome Res 27:512–23
     [Google Scholar]
  4. 4. 
    Allio R, Donega S, Galtier N, Nabholz B 2017. Large variation in the ratio of mitochondrial to nuclear mutation rate across animals: implications for genetic diversity and the use of mitochondrial DNA as a molecular marker. Mol. Biol. Evol. 34:2762–72
     [Google Scholar]
  5. 5. 
    Almuedo-Castillo M, Bläßle A, Mörsdorf D, Marcon L, Soh GH et al. 2018. Scale-invariant patterning by size-dependent inhibition of Nodal signalling. Nat. Cell Biol. 20:1032–42
     [Google Scholar]
  6. 6. 
    Anderson SA, Eisenstat DD, Shi L, Rubenstein JL 1997. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278:474–76
     [Google Scholar]
  7. 7. 
    Arnold AW, Happle R, Itin PH 2010. Superimposed linear psoriasis unmasked by therapy with adalimumab. Eur. J. Dermatol. 20:573–74
     [Google Scholar]
  8. 8. 
    Bae T, Tomasini L, Mariani J, Zhou B, Roychowdhury T et al. 2018. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 359:550–55
     [Google Scholar]
  9. 9. 
    Baroffio A, Dupin E, Le Douarin NM 1991. Common precursors for neural and mesectodermal derivatives in the cephalic neural crest. Development 112:301–5
     [Google Scholar]
  10. 10. 
    Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC et al. 2014. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513:422–25
     [Google Scholar]
  11. 11. 
    Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R et al. 2013. An estimation of the number of cells in the human body. Ann. Hum. Biol. 40:463–71
     [Google Scholar]
  12. 12. 
    Biezuner T, Spiro A, Raz O, Amir S, Milo L et al. 2016. A generic, cost-effective, and scalable cell lineage analysis platform. Genome Res 26:1588–99
     [Google Scholar]
  13. 13. 
    Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S et al. 2016. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538:260–64
     [Google Scholar]
  14. 14. 
    Bocklandt S, Lin W, Sehl ME, Sánchez FJ, Sinsheimer JS et al. 2011. Epigenetic predictor of age. PLOS ONE 6:e14821
     [Google Scholar]
  15. 15. 
    Bulfone A, Puelles L, Porteus MH, Frohman MA, Martin GR, Rubenstein JL 1993. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. J. Neurosci 13:3155–72
     [Google Scholar]
  16. 16. 
    Campos-Ortega JA, Knust E. 1990. Molecular analysis of a cellular decision during embryonic development of Drosophila melanogaster: epidermogenesis or neurogenesis. Eur. J. Biochem. 190:1–10
     [Google Scholar]
  17. 17. 
    Chaisson MJP, Huddleston J, Dennis MY, Sudmant PH, Malig M et al. 2015. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517:608–11
     [Google Scholar]
  18. 18. 
    Chen C, Xing D, Tan L, Li H, Zhou G et al. 2017. Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI). Science 356:189–94
     [Google Scholar]
  19. 19. 
    Chen L, Wang D, Wu Z, Ma L, Daley GQ 2010. Molecular basis of the first cell fate determination in mouse embryogenesis. Cell Res 20:982–93
     [Google Scholar]
  20. 20. 
    Cockburn K, Rossant J. 2010. Making the blastocyst: lessons from the mouse. J. Clin. Investig. 120:995–1003
     [Google Scholar]
  21. 21. 
    Cole LW. 2016. The evolution of per-cell organelle number. Front. Cell Dev. Biol. 4:85
     [Google Scholar]
  22. 22. 
    Doe CQ. 2017. Temporal patterning in the Drosophila CNS. Annu. Rev. Cell Dev. Biol. 33:219–40
     [Google Scholar]
  23. 23. 
    Doe CQ, Technau GM. 1993. Identification and cell lineage of individual neural precursors in the Drosophila CNS. Trends Neurosci 16:510–14
     [Google Scholar]
  24. 24. 
    Dong X, Zhang L, Milholland B, Lee M, Maslov AY et al. 2017. Accurate identification of single-nucleotide variants in whole-genome-amplified single cells. Nat. Methods 14:491–93
     [Google Scholar]
  25. 25. 
    Evrony GD, Lee E, Mehta BK, Benjamini Y, Johnson RM et al. 2015. Cell lineage analysis in human brain using endogenous retroelements. Neuron 85:49–59
     [Google Scholar]
  26. 26. 
    Fellous TG, McDonald SAC, Burkert J, Humphries A, Islam S et al. 2009. A methodological approach to tracing cell lineage in human epithelial tissues. Stem Cells 27:1410–20
     [Google Scholar]
  27. 27. 
    Franco SJ, Gil-Sanz C, Martinez-Garay I, Espinosa A, Harkins-Perry SR et al. 2012. Fate-restricted neural progenitors in the mammalian cerebral cortex. Science 337:746–49
     [Google Scholar]
  28. 28. 
    Fraser S, Keynes R, Lumsden A 1990. Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions. Nature 344:431–35
     [Google Scholar]
  29. 29. 
    Gaiti F, Chaligne R, Gu H, Brand RM, Kothen-Hill S et al. 2019. Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia. Nature 569:576–80
     [Google Scholar]
  30. 30. 
    Gaj T, Perez-Pinera P. 2018. The continuously evolving CRISPR barcoding toolbox. Genome Biol 19:143
     [Google Scholar]
  31. 31. 
    Giangreco A, Arwert EN, Rosewell IR, Snyder J, Watt FM, Stripp BR 2009. Stem cells are dispensable for lung homeostasis but restore airways after injury. PNAS 106:9286–91
     [Google Scholar]
  32. 32. 
    Ginhoux F, Garel S. 2018. The mysterious origins of microglia. Nat. Neurosci. 21:897–99
     [Google Scholar]
  33. 33. 
    Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JLR, Jones KR 2002. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J. Neurosci. 22:6309–14
     [Google Scholar]
  34. 34. 
    Goyal R, Reinhardt R, Jeltsch A 2006. Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase. Nucleic Acids Res 34:1182–88
     [Google Scholar]
  35. 35. 
    Gravina S, Ganapathi S, Vijg J 2015. Single-cell, locus-specific bisulfite sequencing (SLBS) for direct detection of epimutations in DNA methylation patterns. Nucleic Acids Res 43:e93
     [Google Scholar]
  36. 36. 
    Guo H, Zhu P, Wu X, Li X, Wen L, Tang F 2013. Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res 23:2126–35
     [Google Scholar]
  37. 37. 
    Hackett JA, Surani MA. 2013. DNA methylation dynamics during the mammalian life cycle. Philos. Trans. R. Soc. Lond. B 368:20110328
     [Google Scholar]
  38. 38. 
    Halperin SO, Tou CJ, Wong EB, Modavi C, Schaffer DV, Dueber JE 2018. CRISPR-guided DNA polymerases enable diversification of all nucleotides in a tunable window. Nature 560:248–52
     [Google Scholar]
  39. 39. 
    Hayashi S, McMahon AP. 2002. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev. Biol. 244:305–18
     [Google Scholar]
  40. 40. 
    Home P, Saha B, Ray S, Dutta D, Gunewardena S et al. 2012. Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment. PNAS 109:7362–67
     [Google Scholar]
  41. 41. 
    Horsthemke B. 2006. Epimutations in human disease. DNA Methylation: Development, Genetic Disease and Cancer W Doerfler, P Böhm 45–59 Curr. Top. Microbiol. Immunol. 310 Berlin: Springer
     [Google Scholar]
  42. 42. 
    Huang Y, Xu Z, Xiong S, Qin G, Sun F et al. 2018. Dual extra-retinal origins of microglia in the model of retinal microglia repopulation. Cell Discov 4:9
     [Google Scholar]
  43. 43. 
    Hwang B, Lee W, Yum S-Y, Jeon Y, Cho N et al. 2019. Lineage tracing using a Cas9-deaminase barcoding system targeting endogenous L1 elements. Nat. Commun. 10:1234–39
     [Google Scholar]
  44. 44. 
    Jain M, Olsen HE, Paten B, Akeson M 2016. The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics community. Genome Biol 17:239
     [Google Scholar]
  45. 45. 
    Jin B, Li Y, Robertson KD 2011. DNA methylation: superior or subordinate in the epigenetic hierarchy. Genes Cancer 2:607–17
     [Google Scholar]
  46. 46. 
    Jin H, Zhang G, Zhou Y, Chang C, Lu Q 2016. Old lines tell new tales: Blaschko linear lupus erythematosis. Autoimmun. Rev. 15:291–306
     [Google Scholar]
  47. 47. 
    Kalhor R, Kalhor K, Mejia L, Leeper K, Graveline A et al. 2018. Developmental barcoding of whole mouse via homing CRISPR. Science 361:eaat9804
     [Google Scholar]
  48. 48. 
    Kellendonk C, Tronche F, Casanova E, Anlag K, Opherk C, Schütz G 1999. Inducible site-specific recombination in the brain. J. Mol. Biol. 285:175–82
     [Google Scholar]
  49. 49. 
    Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD 2006. Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat. Neurosci. 9:173–79
     [Google Scholar]
  50. 50. 
    Kim K-M, Shibata D. 2004. Tracing ancestry with methylation patterns: most crypts appear distantly related in normal adult human colon. BMC Gastroenterol 4:8–10
     [Google Scholar]
  51. 51. 
    Kohwi M, Doe CQ. 2013. Temporal fate specification and neural progenitor competence during development. Nat. Rev. Neurosci. 14:823–38
     [Google Scholar]
  52. 52. 
    Kretzschmar K, Watt FM. 2012. Lineage tracing. Cell 148:33–45
     [Google Scholar]
  53. 53. 
    Kuijk E, Blokzijl F, Jager M, Besselink N, Boymans S et al. 2019. Early divergence of mutational processes in human fetal tissues. Sci. Adv. 5:eaaw1271
     [Google Scholar]
  54. 54. 
    Lasken RS, Stockwell TB. 2007. Mechanism of chimera formation during the Multiple Displacement Amplification reaction. BMC Biotechnol 7:19
     [Google Scholar]
  55. 55. 
    Le Douarin NM, Dupin E 1993. Cell lineage analysis in neural crest ontogeny. J. Neurobiol. 24:146–61
     [Google Scholar]
  56. 56. 
    Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K et al. 2018. Population dynamics of normal human blood inferred from somatic mutations. Nature 561:473–78
     [Google Scholar]
  57. 57. 
    Lim L, Mi D, Llorca A, Marín O 2018. Development and functional diversification of cortical interneurons. Neuron 100:294–313
     [Google Scholar]
  58. 58. 
    Lister R, Ecker JR. 2009. Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res 19:959–66
     [Google Scholar]
  59. 59. 
    Lodato MA, Rodin RE, Bohrson CL, Coulter ME, Barton AR et al. 2018. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 359:555–59
     [Google Scholar]
  60. 60. 
    Lodato MA, Woodworth MB, Lee S, Evrony GD, Mehta BK et al. 2015. Somatic mutation in single human neurons tracks developmental and transcriptional history. Science 350:94–98
     [Google Scholar]
  61. 61. 
    Ludwig LS, Lareau CA, Ulirsch JC, Christian E, Muus C et al. 2019. Lineage tracing in humans enabled by mitochondrial mutations and single-cell genomics. Cell 176:1325–1339.e22
     [Google Scholar]
  62. 62. 
    Lumsden A. 1991. Cell lineage restrictions in the chick embryo hindbrain. Philos. Trans. R. Soc. B 331:281–86
     [Google Scholar]
  63. 63. 
    Luo G-Z, Blanco MA, Greer EL, He C, Shi Y 2015. DNA N6-methyladenine: a new epigenetic mark in eukaryotes. Nat. Rev. Mol. Cell Biol. 16:705–10
     [Google Scholar]
  64. 64. 
    Luquette LJ, Bohrson CL, Sherman MA, Park PJ 2019. Identification of somatic mutations in single cell DNA-seq using a spatial model of allelic imbalance. Nat. Commun. 10:3908–14
     [Google Scholar]
  65. 65. 
    Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F et al. 2018. Somatic mutant clones colonize the human esophagus with age. Science 362:911–17
     [Google Scholar]
  66. 66. 
    McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T et al. 2013. Mosaic copy number variation in human neurons. Science 342:632–37
     [Google Scholar]
  67. 67. 
    Meissner A, Gnirke A, Bell GW, Ramsahoye B, Lander ES, Jaenisch R 2005. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res 33:5868–77
     [Google Scholar]
  68. 68. 
    Menck CF, Munford V. 2014. DNA repair diseases: What do they tell us about cancer and aging. Genet. Mol. Biol. 37: Suppl. 1 220–33
     [Google Scholar]
  69. 69. 
    Milholland B, Dong X, Zhang L, Hao X, Suh Y, Vijg J 2017. Differences between germline and somatic mutation rates in humans and mice. Nat. Commun. 8:15183
     [Google Scholar]
  70. 70. 
    Miyoshi G, Hjerling-Leffler J, Karayannis T, Sousa VH, Butt SJB et al. 2010. Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J. Neurosci. 30:1582–94
     [Google Scholar]
  71. 71. 
    Mooijman D, Dey SS, Boisset J-C, Crosetto N, van Oudenaarden A 2016. Single-cell 5hmC sequencing reveals chromosome-wide cell-to-cell variability and enables lineage reconstruction. Nat. Biotechnol. 34:852–56
     [Google Scholar]
  72. 72. 
    Moore LD, Le T, Fan G 2013. DNA methylation and its basic function. Neuropsychopharmacology 38:23–38
     [Google Scholar]
  73. 73. 
    Navin N, Kendall J, Troge J, Andrews P, Rodgers L et al. 2011. Tumour evolution inferred by single-cell sequencing. Nature 472:90–94
     [Google Scholar]
  74. 74. 
    Nekhaeva E, Bodyak ND, Kraytsberg Y, McGrath SB, Van Orsouw NJ et al. 2002. Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues. PNAS 99:5521–26
     [Google Scholar]
  75. 75. 
    Nery S, Fishell G, Corbin JG 2002. The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nat. Neurosci. 5:1279–87
     [Google Scholar]
  76. 76. 
    O'Driscoll M. 2012. Diseases associated with defective responses to DNA damage. Cold Spring Harb. Perspect. Biol. 4:a012773
     [Google Scholar]
  77. 77. 
    Paul S, Knott JG. 2014. Epigenetic control of cell fate in mouse blastocysts: the role of covalent histone modifications and chromatin remodeling. Mol. Reprod. Dev. 81:171–82
     [Google Scholar]
  78. 78. 
    Pei W, Wang X, Rössler J, Feyerabend TB, Höfer T, Rodewald H-R 2019. Using Cre-recombinase-driven Polylox barcoding for in vivo fate mapping in mice. Nat. Protoc. 14:1820–40
     [Google Scholar]
  79. 79. 
    Poelmann RE. 1980. Differential mitosis and degeneration patterns in relation to the alterations in the shape of the embryonic ectoderm of early post-implantation mouse embryos. J. Embryol. Exp. Morphol. 55:33–51
     [Google Scholar]
  80. 80. 
    Popp C, Dean W, Feng S, Cokus SJ, Andrews S et al. 2010. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463:1101–5
     [Google Scholar]
  81. 81. 
    Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB et al. 2016. Timing, rates and spectra of human germline mutation. Nat. Genet. 48:126–33
     [Google Scholar]
  82. 82. 
    Regev A, Teichmann SA, Lander ES, Amit I, Benoist C et al. 2017. The Human Cell Atlas. eLife 6:e27041
     [Google Scholar]
  83. 83. 
    Rhoads A, Au KF. 2015. PacBio sequencing and its applications. Genom. Proteom. Bioinform. 13:278–89
     [Google Scholar]
  84. 84. 
    Riggs AD, Xiong Z. 2004. Methylation and epigenetic fidelity. PNAS 101:4–5
     [Google Scholar]
  85. 85. 
    Robin ED, Wong R. 1988. Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J. Cell. Physiol. 136:507–13
     [Google Scholar]
  86. 86. 
    Rubenstein JL, Martinez S, Shimamura K, Puelles L 1994. The embryonic vertebrate forebrain: the prosomeric model. Science 266:578–80
     [Google Scholar]
  87. 87. 
    Salas LA, Wiencke JK, Koestler DC, Zhang Z, Christensen BC, Kelsey KT 2018. Tracing human stem cell lineage during development using DNA methylation. Genome Res 28:1285–95
     [Google Scholar]
  88. 88. 
    Shibata D. 2009. Inferring human stem cell behaviour from epigenetic drift. J. Pathol. 217:199–205
     [Google Scholar]
  89. 89. 
    Smith ZD, Meissner A. 2013. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14:204–20
     [Google Scholar]
  90. 90. 
    Snow MHL. 1977. Gastrulation in the mouse: growth and regionalization of the epiblast. Development 42:293–303
     [Google Scholar]
  91. 91. 
    Sugimoto S, Ohta Y, Fujii M, Matano M, Shimokawa M et al. 2018. Reconstruction of the human colon epithelium in vivo. Cell Stem Cell 22:171–75
     [Google Scholar]
  92. 92. 
    Taylor RW, Barron MJ, Borthwick GM, Gospel A, Chinnery PF et al. 2003. Mitochondrial DNA mutations in human colonic crypt stem cells. J. Clin. Investig. 112:1351–60
     [Google Scholar]
  93. 93. 
    Teixeira VH, Nadarajan P, Graham TA, Pipinikas CP, Brown JM et al. 2013. Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors. eLife 2:e00966
     [Google Scholar]
  94. 94. 
    Trapnell C. 2015. Defining cell types and states with single-cell genomics. Genome Res 25:1491–98
     [Google Scholar]
  95. 95. 
    Ushijima T, Watanabe N, Okochi E, Kaneda A, Sugimura T, Miyamoto K 2003. Fidelity of the methylation pattern and its variation in the genome. Genome Res 13:868–74
     [Google Scholar]
  96. 96. 
    Vickaryous MK, Hall BK. 2006. Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Biol. Rev. Camb. Philos. Soc. 81:425–55
     [Google Scholar]
  97. 97. 
    Walther V, Alison MR. 2016. Cell lineage tracing in human epithelial tissues using mitochondrial DNA mutations as clonal markers. Wiley Interdiscip. Rev. Dev. Biol. 5:103–17
     [Google Scholar]
  98. 98. 
    Willems T, Gymrek M, Poznik GD, Tyler-Smith C 2016. Population-scale sequencing data enable precise estimates of Y-STR mutation rates. Am. J. Hum. Genet 98:919–33
     [Google Scholar]
  99. 99. 
    Wilson DJ, Hinchliffe JR. 1987. The effect of the zone of polarizing activity (ZPA) on the anterior half of the chick wing bud. Development 99:99–108
     [Google Scholar]
  100. 100. 
    Wizenmann A, Lumsden A. 1997. Segregation of rhombomeres by differential chemoaffinity. Mol. Cell. Neurosci. 9:448–59
     [Google Scholar]
  101. 101. 
    Xiao C-L, Zhu S, He M, Chen D, Zhang Q et al. 2018. N6-methyladenine DNA modification in the human genome. Mol. Cell 71:306–18.e7
     [Google Scholar]
  102. 102. 
    Xu J, Nuno K, Litzenburger UM, Qi Y, Corces MR et al. 2019. Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA. eLife 8:e45105
     [Google Scholar]
  103. 103. 
    Xu Q, Tam M, Anderson SA 2008. Fate mapping Nkx2.1-lineage cells in the mouse telencephalon. J. Comp. Neurol. 506:16–29
     [Google Scholar]
  104. 104. 
    Yatabe Y, Tavaré S, Shibata D 2001. Investigating stem cells in human colon by using methylation patterns. PNAS 98:10839–44
     [Google Scholar]
/content/journals/10.1146/annurev-genom-083118-015241
Loading
Cell Lineage Tracing and Cellular Diversity in Humans
Annual Review of Genomics and Human Genetics 21, 101 (2020); https://doi.org/10.1146/annurev-genom-083118-015241
/content/journals/10.1146/annurev-genom-083118-015241
/content/journals/10.1146/annurev-genom-083118-015241
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

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