Colon Stem Cell and Crypt Dynamics Exposed by Cell Lineage Reconstruction

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Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.

Vyšlo v časopise: Colon Stem Cell and Crypt Dynamics Exposed by Cell Lineage Reconstruction. PLoS Genet 7(7): e32767. doi:10.1371/journal.pgen.1002192
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002192

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1. SternCFraserS 2001 Tracing the lineage of tracing cell lineages. Nat Cell Biol 3 E216 218

2. SnippertHvan der FlierLSatoTvan EsJvan den BornM 2010 Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143 134 144

3. DorYBrownJMartinezOMeltonD 2004 Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429 41 46

4. FrumkinDWasserstromAKaplanSFeigeUShapiroE 2005 Genomic variability within an organism exposes its cell lineage tree. PLoS Comput Biol 1 e50 doi:10.1371/journal.pcbi.0010050

5. FrumkinDWasserstromAItzkovitzSSternTHarmelinA 2008 Cell lineage analysis of a mouse tumor. Cancer Res 68 5924 5931

6. WasserstromAFrumkinDAdarRItzkovitzSSternT 2008 Estimating cell depth from somatic mutations. PLoS Comput Biol 4 e1000058 doi:10.1371/journal.pcbi.1000058

7. WasserstromAAdarRSheferGFrumkinDItzkovitzS 2008 Reconstruction of cell lineage trees in mice. PLoS ONE 3 e1939 doi:10.1371/journal.pone.0001939

8. SalipanteSHorwitzM 2006 Phylogenetic fate mapping. Proc Natl Acad Sci U S A 103 5448 5453

9. SalipanteSHorwitzM 2007 A phylogenetic approach to mapping cell fate. Curr Top Dev Biol 79 157 184

10. SalipanteSThompsonJHorwitzM 2008 Phylogenetic fate mapping: theoretical and experimental studies applied to the development of mouse fibroblasts. Genetics 178 967 977

11. SalipanteSKasAMcMonagleEHorwitzM 2010 Phylogenetic analysis of developmental and postnatal mouse cell lineages. Evol Dev 12 84 94

12. ShriverMDJinLBoerwinkleEDekaRFerrellRE 1995 A novel measure of genetic distance for highly polymorphic tandem repeat loci. Mol Biol Evol 12 914 920

13. BakerSMPlugAWProllaTABronnerCEHarrisAC 1996 Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet 13 336 342

14. BarkerNvan EsJKuipersJKujalaPvan den BornM 2007 Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449 1003 1007

15. BarkerNvan de WeteringMCleversH 2008 The intestinal stem cell. Genes Dev 22 1856 1864

16. BarkerNvan EsJJaksVKasperMSnippertH 2008 Very long-term self-renewal of small intestine, colon, and hair follicles from cycling Lgr5+ve stem cells. Cold Spring Harb Symp Quant Biol 73 351 356

17. CleversH 2005 Stem cells, asymmetric division and cancer. Nat Genet 37 1027 1028

18. CleversH 2009 Searching for adult stem cells in the intestine. EMBO Mol Med 1 255 259

19. RadtkeFCleversH 2005 Self-renewal and cancer of the gut: two sides of a coin. Science 307 1904 1909

20. Lopez-GarciaCKleinAMSimonsBDWintonDJ 2010 Intestinal stem cell replacement follows a pattern of neutral drift. Science 330 822 825

21. SchepersAGVriesRvan den BornMvan de WeteringMCleversH 2011 Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes. EMBO J

22. GordonJSchmidtGRothK 1992 Studies of intestinal stem cells using normal, chimeric, and transgenic mice. FASEB J 6 3039 3050

23. SchmidtGHWilkinsonMMPonderBA 1985 Detection and characterization of spatial pattern in chimaeric tissue. J Embryol Exp Morphol 88 219 230

24. SchmidtGHWintonDJPonderBA 1988 Development of the pattern of cell renewal in the crypt-villus unit of chimaeric mouse small intestine. Development 103 785 790

25. WintonDBlountMPonderB 1988 A clonal marker induced by mutation in mouse intestinal epithelium. Nature 333 463 466

26. HermistonMGordonJ 1995 Organization of the crypt-villus axis and evolution of its stem cell hierarchy during intestinal development. Am J Physiol 268 G813 822

27. RothKHermistonMGordonJ 1991 Use of transgenic mice to infer the biological properties of small intestinal stem cells and to examine the lineage relationships of their descendants. Proc Natl Acad Sci U S A 88 9407 9411

28. CairnsJ 1975 Mutation selection and the natural history of cancer. Nature 255 197 200

29. CairnsJ 2006 Cancer and the immortal strand hypothesis. Genetics 174 1069 1072

30. KarpowiczPMorsheadCKamAJervisERamunasJ 2005 Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro. J Cell Biol 170 721 732

31. LewDBurkeDDuttaA 2008 The immortal strand hypothesis: how could it work? Cell 133 21 23

32. RandoT 2007 The immortal strand hypothesis: segregation and reconstruction. Cell 129 1239 1243

33. ShininVGayraud-MorelBGomèsDTajbakhshS 2006 Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nat Cell Biol 8 677 687

34. WaltersK 2009 Colonic stem cell data are consistent with the immortal model of stem cell division under non-random strand segregation. Cell Prolif 42 339 347

35. PottenCOwenGBoothD 2002 Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 115 2381 2388

36. ConboyMKarasovARandoT 2007 High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny. PLoS Biol 5 e102 10.1371/journal.pbio.0050102

37. NovelliMCossuAOukrifDQuagliaALakhaniS 2003 X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. Proc Natl Acad Sci U S A 100 3311 3314

38. KrauseDTheiseNCollectorMHenegariuOHwangS 2001 Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105 369 377

39. KörblingMKatzRKhannaARuifrokARondonG 2002 Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 346 738 746

40. AbkowitzJ 2002 Can human hematopoietic stem cells become skin, gut, or liver cells? N Engl J Med 346 770 772

41. SchmidtGWintonDPonderB 1988 Development of the pattern of cell renewal in the crypt-villus unit of chimaeric mouse small intestine. Development 103 785 790

42. FulcherDABastenA 1997 B cell life span: a review. Immunol Cell Biol 75 446 455

43. SunTTTsengSCLavkerRM 2010 Location of corneal epithelial stem cells. Nature 463 E10 11; discussion E11

44. MajoFRochatANicolasMJaoudéGABarrandonY 2008 Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature 456 250 254

45. FrumkinDWasserstromAItzkovitzSHarmelinARechaviG 2008 Amplification of multiple genomic loci from single cells isolated by laser micro-dissection of tissues. BMC Biotechnol 8 17

46. KumarGGarnovaEReaginMVidaliA 2008 Improved multiple displacement amplification with phi29 DNA polymerase for genotyping of single human cells. Biotechniques 44 879 890

47. SaitouNNeiM 1987 The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4 406 425