期刊
CELL REPORTS
卷 20, 期 7, 页码 1609-1622出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.07.061
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资金
- Royal College of Surgeons of England
- Cancer Research UK Clinician Scientist Fellowship [C10169/A12173]
- Wellcome Trust [098357/Z/12/Z, 110326/Z/15/Z, 096919/Z/11/Z]
- Trinity College, Cambridge
- Wellcome Trust
- Medical Research Council (MRC) Centre for Neuromuscular Diseases [G0601943]
- Lily Foundation
- UK National Health Service (NHS) Highly Specialised Rare Mitochondrial Disorders of Adults and Children'' Service
- Newcastle University Centre for Ageing and Vitality - Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council (EPSRC)
- Economic and Social Research Council (ESRC)
- MRC as part of the crosscouncil Lifelong Health and Wellbeing Initiative
- Cancer Research UK [16485, 14895, 12173] Funding Source: researchfish
- Medical Research Council [G0601943, G0700718, MR/L016354/1, MC_PC_15065, MC_PC_12009] Funding Source: researchfish
- NIHR Newcastle Biomedical Research Centre [BH111030] Funding Source: researchfish
- MRC [G0601943, MC_PC_15065, MR/L016354/1, G0700718] Funding Source: UKRI
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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