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Development, maturation, and maintenance of human prostate inferred from somatic mutations

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.

Publication metadata

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


DOI: 10.1016/j.stem.2021.02.005

PubMed id: 33657416


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Funder referenceFunder name
18CHAL11Prostate Cancer Foundation