Journal
NATURE GENETICS
Volume 52, Issue 9, Pages 908-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-020-0642-1
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Funding
- National Key Research and Development Program of China [2017YFA0505500]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16020905, XDB19000000]
- National Natural Science Foundation of China [81830054, 81772723, 61403363, 11901272]
- State Key Project for Infectious Diseases [2018ZX10302207-004-002]
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
- US National Cancer Institute [R01CA208100, R01CA193837, P50CA092629, P30CA008748]
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The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked byTacstd2,Ck4andPscaexpression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion ofPtenin Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer. Single-cell RNA-seq and in vivo lineage tracing identify unique luminal progenitors in the mouse prostate that can contribute to regeneration and oncogenesis. Single-cell RNA-seq analysis of human prostate identifies a similar cell population.
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