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Lookup NU author(s): Laura WilsonORCiD, Professor Rakesh Heer
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Authors. Clonal dynamics and mutation burden in healthy human prostate epithelium are relevant to prostate cancer. We sequenced whole genomes from 409 microdissections of normal prostate epithelium across 8 donors, using phylogenetic reconstruction with spatial mapping in a 59-year-old man's prostate to reconstruct tissue dynamics across the lifespan. Somatic mutations accumulate steadily at ∼16 mutations/year/clone, with higher rates in peripheral than peri-urethral regions. The 24–30 independent glandular subunits are established as rudimentary ductal structures during fetal development by 5–10 embryonic cells each. Puberty induces formation of further side and terminal branches by local stem cells disseminated throughout the rudimentary ducts during development. During adult tissue maintenance, clonal expansions have limited geographic scope and minimal migration. Driver mutations are rare in aging prostate epithelium, but the one driver we did observe generated a sizable intraepithelial clonal expansion. Leveraging unbiased clock-like mutations, we define prostate stem cell dynamics through fetal development, puberty, and aging. Using spontaneously occurring somatic mutations as lineage marks, Campbell, Heer, and colleagues define the stem cell dynamics of normal human prostate epithelium through fetal development, puberty, adulthood, and aging.
Author(s): Grossmann S, Hooks Y, Wilson L, Moore L, O'Neill L, Martincorena I, Voet T, Stratton MR, Heer R, Campbell PJ
Publication type: Article
Publication status: Published
Journal: Cell Stem Cell
Year: 2021
Volume: 28
Issue: 7
Pages: 1262-1274.e5
Print publication date: 01/07/2021
Online publication date: 02/03/2021
Acceptance date: 02/02/2021
Date deposited: 07/04/2021
ISSN (print): 1934-5909
ISSN (electronic): 1875-9777
Publisher: Cell Press
URL: https://doi.org/10.1016/j.stem.2021.02.005
DOI: 10.1016/j.stem.2021.02.005
PubMed id: 33657416
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