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

Baker, A-M; Cereser, B; Melton, S; Fletcher, AG; Rodriguez-Justo, M; Tadrous, PJ; Humphries, A; ... Graham, TA; + view all (2014) Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon. Cell Reports , 8 (4) pp. 940-947. 10.1016/j.celrep.2014.07.019. Green open access

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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.

Type: Article
Title: Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2014.07.019
Publisher version: https://doi.org/10.1016/j.celrep.2014.07.019
Language: English
Additional information: © 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10074995
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