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

Stem Cell Reports. 2019 Jun 11;12(6):1201-1211. doi: 10.1016/j.stemcr.2019.04.019. Epub 2019 May 23.

Abstract

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.

Keywords: Nestin; mesenchymal-to-epithelial transition; prostate stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / biosynthesis*
  • Antigens / genetics
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Gene Expression Regulation / radiation effects
  • Male
  • Mice
  • Mice, Transgenic
  • Nestin / biosynthesis*
  • Nestin / genetics
  • Organ Transplantation*
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostate / transplantation*
  • Proteoglycans / biosynthesis*
  • Proteoglycans / genetics
  • Radiation Injuries, Experimental* / metabolism
  • Radiation Injuries, Experimental* / pathology
  • Radiation Injuries, Experimental* / surgery
  • Radiation Tolerance*
  • Stem Cells / metabolism*
  • Stem Cells / pathology

Substances

  • Antigens
  • Nes protein, mouse
  • Nestin
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4