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Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts

Lookup NU author(s): Dr Craig Stamp, Dr Anze Zupanic, Ashwin Sachdeva, Dr Elizabeth Stoll, Dr Daryl Shanley, Professor John Mathers, Emeritus Professor Thomas Kirkwood, Professor Rakesh Heer, Emeritus Professor Doug Turnbull, Dr Laura Greaves



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 The Authors Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal crypts across the adult life-course. By resolving the frequency and size distribution of OXPHOS-deficient clones, quantitative analysis shows that, in common with mouse, long-term maintenance of the colonic epithelial crypt relies on stochastic SC loss and replacement mediated by competition for limited niche access. We find that the colonic crypt is maintained by ~5 effective SCs. However, with a SC loss/replacement rate estimated to be slower than once per year, our results indicate that the vast majority of individual SC divisions result in asymmetric fate outcome. These findings provide a quantitative platform to detect and study deviations from human colorectal crypt SC niche homeostasis during the process of colorectal carcinogenesis.

Publication metadata

Author(s): Stamp C, Zupanic A, Sachdeva A, Stoll EA, Shanley DP, Mathers JC, Kirkwood TBL, Heer R, Simons BD, Turnbull DM, Greaves LC

Publication type: Article

Publication status: Published

Journal: EBioMedicine

Year: 2018

Volume: 31

Pages: 166-173

Print publication date: 01/05/2018

Online publication date: 25/04/2018

Acceptance date: 19/04/2018

Date deposited: 04/06/2018

ISSN (electronic): 2352-3964

Publisher: Elsevier BV


DOI: 10.1016/j.ebiom.2018.04.017


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Funder referenceFunder name
BB/008200/1Biotechnology and Biological Sciences Research Council (BBSRC)
DMT: IS-BRC-1215-20001