Nicholson, AM, Olpe, C, Hoyle, A et al. (17 more authors) (2018) Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium. Cell Stem Cell, 22 (6). 909-918.e8. ISSN 1934-5909
Abstract
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Keywords: | human; colon; epithelium; crypt; stem cells; dynamics; mutation; clone; fission; expansion |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Apr 2018 11:08 |
Last Modified: | 25 Jun 2023 21:19 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.stem.2018.04.020 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:130091 |
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