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Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

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Title: Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon
Author(s): Baker, AM
Cereser, B
Melton, S
Fletcher, AG
Rodriguez-Justo, M
Tadrous, PJ
Humphries, A
Elia, G
McDonald, SA
Wright, NA
Simons, BD
Jansen, M
Graham, TA
Item Type: Journal Article
Abstract: Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a "functional" stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC(-/+)). Furthermore, we show that, in adenomatous crypts (APC(-/-)), there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30-40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.
Publication Date: 7-Aug-2014
Date of Acceptance: 15-Jul-2014
URI: http://hdl.handle.net/10044/1/39950
DOI: http://dx.doi.org/10.1016/j.celrep.2014.07.019
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 940
End Page: 947
Journal / Book Title: Cell Reports
Volume: 8
Issue: 4
Copyright Statement: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Keywords: Aberrant Crypt Foci
Adenomatous Polyposis Coli
Adult Stem Cells
Base Sequence
Case-Control Studies
Cell Differentiation
Cell Proliferation
Colon
DNA Mutational Analysis
Humans
Intestinal Mucosa
Mutation
Intestinal Mucosa
Colon
Humans
Adenomatous Polyposis Coli
Case-Control Studies
DNA Mutational Analysis
Cell Differentiation
Cell Proliferation
Base Sequence
Mutation
Adult Stem Cells
Aberrant Crypt Foci
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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