Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate

• Published in: Stem cell reports Vol. 12; no. 6; pp. 1201 - 1211
• Main Authors: Hanoun, Maher, Arnal-Estapé, Anna, Maryanovich, Maria, Zahalka, Ali H., Bergren, Sarah K., Chua, Chee W., Leftin, Avigdor, Brodin, Patrik N., Shen, Michael M., Guha, Chandan, Frenette, Paul S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.06.2019; Elsevier
• Subjects: Animals; Antigens - biosynthesis; Antigens - genetics; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gene Expression Regulation - radiation effects; Male; mesenchymal-to-epithelial transition; Mice; Mice, Transgenic; Nestin; Nestin - biosynthesis; Nestin - genetics; Organ Transplantation; Prostate - metabolism; Prostate - pathology; Prostate - transplantation; prostate stem cell; Proteoglycans - biosynthesis; Proteoglycans - genetics; Radiation Injuries, Experimental - metabolism; Radiation Injuries, Experimental - pathology; Radiation Injuries, Experimental - surgery; Radiation Tolerance; Stem Cells - metabolism; Stem Cells - pathology; prostate stem cell; Nestin; mesenchymal-to-epithelial transition
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2019.04.019

In the prostate, stem and progenitor cell regenerative capacities have been ascribed to both basal and luminal epithelial cells. Here, we show that a rare subset of mesenchymal cells in the prostate are epithelial-primed Nestin-expressing cells (EPNECs) that can generate self-renewing prostate organoids with bipotential capacity. Upon transplantation, these EPNECs can form prostate gland tissue grafts at the clonal level. Lineage-tracing analyses show that cells marked by Nestin or NG2 transgenic mice contribute to prostate epithelium during organogenesis. In the adult, modest contributions in repeated rounds of regression and regeneration are observed, whereas prostate epithelial cells derived from Nestin/NG2-marked cells are dramatically increased after severe irradiation-induced organ damage. These results indicate that Nestin/NG2 expression marks a novel radioresistant prostate stem cell that is active during development and displays reserve stem cell activity for tissue maintenance. [Display omitted] •The murine prostate mesenchyme contains epithelial-primed Nestin+ cells•Nestin+ cells generate self-renewing prostate organoids and glands at clonal level•NG2/Nestin+ cells contribute to prostate epithelium during organogenesis•NG2/Nestin+ cells retain reserve stem cell activity for tissue regeneration in the adult In this article, Frenette and colleagues show that Nestin/NG2-expressing cells contribute to prostate epithelium during organogenesis and retain reserve stem cell activity during severe irradiation-induced tissue damage while epithelial-primed Nestin-expressing cells maintain bilineage epithelial differentiation potential in the unperturbed adult prostate.