Browse by author
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.
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
URL: https://doi.org/10.1016/j.ebiom.2018.04.017
DOI: 10.1016/j.ebiom.2018.04.017
Altmetrics provided by Altmetric
