Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates | Zendy

Mohammad Moad | Zendy; Édouard Hannezo | Zendy; Simon J.A. Buczacki | Zendy; Laura Wilson | Zendy; Amira ElSherif | Zendy; David Sims | Zendy; Robert Pickard | Zendy; Nicholas A. Wright | Zendy; Stuart C. Williamson | Zendy; Douglass M. Turnbull | Zendy; Robert W. Taylor | Zendy; Laura C. Greaves | Zendy; Craig Robson | Zendy; Benjamin D. Simons | Zendy; Rakesh Heer | Zendy

Open Access

Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates

Author(s) -

Mohammad Moad,

Édouard Hannezo,

Simon J.A. Buczacki,

Laura Wilson,

Amira ElSherif,

David Sims,

Robert Pickard,

Nicholas A. Wright,

Stuart C. Williamson,

Douglass M. Turnbull,

Robert W. Taylor,

Laura C. Greaves,

Craig Robson,

Benjamin D. Simons,

Rakesh Heer

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.07.061

Subject(s) - stem cell , biology , progenitor cell , microbiology and biotechnology , multipotent stem cell , progenitor , basal (medicine) , adult stem cell , niche , lineage (genetic) , cellular differentiation , anatomy , genetics , gene , endocrinology , insulin , ecology

Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1) enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.

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