Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon
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Published version
Author(s)
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.
Date Issued
2014-08-07
Date Acceptance
2014-07-15
Citation
Cell Reports, 2014, 8 (4), pp.940-947
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/).
Subjects
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
Publication Status
Published