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Cell Rep. 2017 Aug 15;20(7):1609-1622. doi: 10.1016/j.celrep.2017.07.061.

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

Author information

1
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4AD, UK.
2
Cavendish Laboratory, Department of Physics, University of Cambridge, J.J. Thomson Avenue, Cambridge CB3 0HE, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
3
Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
4
Department of Histopathology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK; Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
5
Computational Genomics Analysis and Training (CGAT), MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
6
Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
7
Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
8
Clinical and Experimental Pharmacology Group, University of Manchester, Manchester M13 9PL, UK.
9
Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Newcastle Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
10
Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
11
Cavendish Laboratory, Department of Physics, University of Cambridge, J.J. Thomson Avenue, Cambridge CB3 0HE, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Wellcome Trust/Medical Research Council Stem Cell Institute, Cambridge CB2 1QR, UK. Electronic address: bds10@cam.ac.uk.
12
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4AD, UK. Electronic address: rakesh.heer@ncl.ac.uk.

Abstract

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.

KEYWORDS:

DLK1; Notch; basal; branch; epithelium; luminal; niche; organoids; prostate; prostate cancer; stem cell

PMID:
28813673
PMCID:
PMC5565638
DOI:
10.1016/j.celrep.2017.07.061
[Indexed for MEDLINE]
Free PMC Article

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