Retinoblastoma Intrinsically Regulates Niche Cell Quiescence, Identity, and Niche Number in the Adult Drosophila Testis

Cell Rep. 2018 Sep 25;24(13):3466-3476.e8. doi: 10.1016/j.celrep.2018.08.083.

Abstract

Homeostasis in adult tissues depends on the precise regulation of stem cells and their surrounding microenvironments, or niches. Here, we show that the cell cycle inhibitor and tumor suppressor Retinoblastoma (RB) is a critical regulator of niche cells in the Drosophila testis. The testis contains a single niche, composed of somatic hub cells, that signals to adjacent germline and somatic stem cells. Hub cells are normally quiescent, but knockdown of the RB homolog Rbf in these cells causes them to proliferate and convert to somatic stem cells. Over time, mutant hub cell clusters enlarge and split apart, forming ectopic hubs surrounded by active stem cells. Furthermore, we show that Rbf's ability to restrict niche number depends on the transcription factors E2F and Escargot and the adhesion molecule E-cadherin. Together this work reveals how precise modulation of niche cells, not only the stem cells they support, can drive regeneration and disease.

Keywords: Drosophila testis; Retinoblastoma; cel quiescence; cell fate conversion; hub cell; live imaging; niche cell; niche fission; stem cell niche; transdifferentiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cell Proliferation
  • Cell Self Renewal*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Male
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Stem Cell Niche*
  • Testis / cytology
  • Testis / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cadherins
  • Drosophila Proteins
  • E2f1 protein, Drosophila
  • Rbf protein, Drosophila
  • Retinoblastoma Protein
  • Transcription Factors
  • esg protein, Drosophila