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

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Mohammad Moad, Edouard Hannezo, Simon J. Buczacki, Laura Wilson, Amira El-Sherif, David Sims, Robert Pickard, Nicholas A. Wright, Stuart C. Williamson, Doug M. Turnbull, Robert W. Taylor, Laura Greaves, Craig N. Robson, Benjamin D. Simons, Rakesh Heer
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.

Graphical abstract

Teaser

Moad et al. find that multipotent prostate basal stem cells, marked by delta homolog 1 (DLK1), reside in proximal ducts and generate directed large-scale epithelial flows traversing the entire length of the branching gland network. This work describes mechanisms underlying 3D epithelial homeostasis in a complex branching tissue.


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