DOI: 10.1186/1741-7015-3-10. Age-related human small intestine methylation: evidence for stem cell niches

10.1186/1741-7015-3-10

Crossref journal-article

Springer Science and Business Media LLC

BMC Medicine (297)

Abstract

Abstract Background The small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells. Very little is known about human small intestines because mouse fate mapping strategies are impractical in humans. However, it is theoretically possible that stem cell histories are inherently written within their genomes. Genomes appear to record histories (as exemplified by use of molecular clocks), and therefore it may be possible to reconstruct somatic cell dynamics from somatic cell errors. Recent human colon studies suggest that random somatic epigenetic errors record stem cell histories (ancestry and total numbers of divisions). Potentially age-related methylation also occurs in human small intestines, which would allow characterization of their stem cells and comparisons with the colon. Methods Methylation patterns in individual crypts from 13 small intestines (17 to 78 years old) were measured by bisulfite sequencing. The methylation patterns were analyzed by a quantitative model to distinguish between immortal or niche stem cell lineages. Results Age-related methylation was observed in the human small intestines. Crypt methylation patterns were more consistent with stem cell niches than immortal stem cell lineages. Human large and small intestine crypt niches appeared to have similar stem cell dynamics, but relatively less methylation accumulated with age in the small intestines. There were no apparent stem cell differences between the duodenum and ileum, and stem cell survival did not appear to decline with aging. Conclusion Crypt niches containing multiple stem cells appear to maintain human small intestines. Crypt niches appear similar in the colon and small intestine, and the small intestinal stem cell mitotic rate is the same as or perhaps slower than that of the colon. Although further studies are needed, age-related methylation appears to record somatic cell histories, and a somatic epigenetic molecular clock strategy may potentially be applied to other human tissues to reconstruct otherwise occult stem cell histories.

Bibliography

Kim, J. Y., Siegmund, K. D., TavarÃ©, S., & Shibata, D. (2005). Age-related human small intestine methylation: evidence for stem cell niches. BMC Medicine, 3(1).

Authors 4

Jung Yeon Kim (first)
Kimberly D Siegmund (additional)
Simon Tavaré (additional)
Darryl Shibata (additional)

References 21 Referenced 56

Gore RM: Small bowel cancer. Clinical and pathologic features. Radiol Clin North Am. 1997, 35: 351-360. (10.1016/S0033-8389(22)00712-6) / Radiol Clin North Am by RM Gore (1997)
Potten CS, Booth C, Hargreaves D: The small intestine as a model for evaluating adult tissue stem cell drug targets. Cell Prolif. 2003, 36: 115-129. 10.1046/j.1365-2184.2003.00264.x. (10.1046/j.1365-2184.2003.00264.x) / Cell Prolif by CS Potten (2003)
Potten CS: Radiation, the ideal cytotoxic agent for studying the cell biology of tissues such as the small intestine. Radiat Res. 2004, 161: 123-136. (10.1667/RR3104) / Radiat Res by CS Potten (2004)
Potten CS, Loeffler M: Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990, 110: 1001-1020. (10.1242/dev.110.4.1001) / Development by CS Potten (1990)
Williams ED, Lowes AP, Williams D, Williams GT: A stem cell niche theory of intestinal crypt maintenance based on a study of somatic mutation in colonic mucosa. Am J Pathol. 1992, 141: 773-776. / Am J Pathol by ED Williams (1992)
Spradling A, Drummond-Barbosa D, Kai T: Stem cells find their niche. Nature. 2001, 414: 98-104. 10.1038/35102160. (10.1038/35102160) / Nature by A Spradling (2001)
Marshman E, Booth C, Potten CS: The intestinal epithelial stem cell. BioEssays. 2002, 24: 91-98. 10.1002/bies.10028. (10.1002/bies.10028) / BioEssays by E Marshman (2002)
Campbell F, Williams GT, Appleton MA, Dixon MF, Harris M, Williams ED: Post-irradiation somatic mutation and clonal stabilisation time in the human colon. Gut. 1996, 39: 569-573. (10.1136/gut.39.4.569) / Gut by F Campbell (1996)
Blair Hedges S, Kumar S: Genomic clocks and evolutionary timescales. Trends Genet. 2003, 19: 200-206. 10.1016/S0168-9525(03)00053-2. (10.1016/S0168-9525(03)00053-2) / Trends Genet by S Blair Hedges (2003)
Yatabe Y, Tavaré S, Shibata D: Investigating stem cells in human colon by using methylation patterns. Proc Natl Acad Sci USA. 2001, 98: 10839-10844. 10.1073/pnas.191225998. (10.1073/pnas.191225998) / Proc Natl Acad Sci USA by Y Yatabe (2001)
Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP: Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res. 1998, 58: 5489-5494. / Cancer Res by N Ahuja (1998)
Issa JP: CpG-island methylation in aging and cancer. Curr Top Microbiol Immunol. 2000, 249: 101-118. / Curr Top Microbiol Immunol by JP Issa (2000)
Bird A: DNA methylation patterns and epigenetic memory. Genes Dev. 2002, 16: 6-21. 10.1101/gad.947102. (10.1101/gad.947102) / Genes Dev by A Bird (2002)
Potten CS, Kellett M, Rew DA, Roberts SA: Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli. Gut. 1992, 33: 524-529. (10.1136/gut.33.4.524) / Gut by CS Potten (1992)
Scott H, Brandtzaeg P: Enumeration of Paneth cells in coeliac disease: comparison of conventional light microscopy and immunofluorescence staining for lysozyme. Gut. 1981, 22: 812-816. (10.1136/gut.22.10.812) / Gut by H Scott (1981)
Garabedian EM, Roberts LJ, McNevin MS, Gordon JI: Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J Biol Chem. 1997, 272: 23729-23740. 10.1074/jbc.272.38.23729. (10.1074/jbc.272.38.23729) / J Biol Chem by EM Garabedian (1997)
Kim KM, Calabrese P, Tavaré S, Shibata D: Enhanced stem cell survival in familial adenomatous Polyposis. Am J Pathol. 2004, 164: 1369-1377. (10.1016/S0002-9440(10)63223-3) / Am J Pathol by KM Kim (2004)
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Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF: Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992, 256: 668-670. (10.1126/science.1350108) / Science by LK Su (1992)

Dates

Type	When
Created	20 years, 2 months ago (June 23, 2005, 2:13 p.m.)
Deposited	10 months, 2 weeks ago (Oct. 7, 2024, 8:56 a.m.)
Indexed	1 month, 1 week ago (July 14, 2025, 11:29 p.m.)
Issued	20 years, 2 months ago (June 23, 2005)
Published	20 years, 2 months ago (June 23, 2005)
Published Online	20 years, 2 months ago (June 23, 2005)

Funders 0

None

BibTeX

@article{Kim_2005, title={Age-related human small intestine methylation: evidence for stem cell niches}, volume={3}, ISSN={1741-7015}, url={http://dx.doi.org/10.1186/1741-7015-3-10}, DOI={10.1186/1741-7015-3-10}, number={1}, journal={BMC Medicine}, publisher={Springer Science and Business Media LLC}, author={Kim, Jung Yeon and Siegmund, Kimberly D and Tavaré, Simon and Shibata, Darryl}, year={2005}, month=jun }

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