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

Leah J. Greenspan, Erika Matunis

Research output: Contribution to journalArticle

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. Greenspan and Matunis find that the tumor suppressor Retinoblastoma is required in niche cells to maintain quiescence, cell fate, and niche number. Loss of Retinoblastoma causes niche cell divisions, conversion to somatic stem cells, and ectopic niche formation through niche fission, suggesting that mutations in niche cells may drive disease.

Original languageEnglish (US)
Pages (from-to)3466-3476.e8
JournalCell Reports
Volume24
Issue number13
DOIs
StatePublished - Sep 25 2018

Keywords

  • cel quiescence
  • cell fate conversion
  • Drosophila testis
  • hub cell
  • live imaging
  • niche cell
  • niche fission
  • Retinoblastoma
  • stem cell niche
  • transdifferentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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