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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.

Original publication




Journal article


Cell Rep

Publication Date





1609 - 1622


DLK1, Notch, basal, branch, epithelium, luminal, niche, organoids, prostate, prostate cancer, stem cell, Biomarkers, Cell Differentiation, Cell Lineage, DNA, Mitochondrial, Epithelial Cells, Gene Expression, Humans, Intercellular Signaling Peptides and Proteins, Laser Capture Microdissection, Male, Membrane Proteins, Multipotent Stem Cells, Primary Cell Culture, Prostate, RNA, Spheroids, Cellular, Stem Cell Niche