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

Summary 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. Graphical Abstract Highlights • Loss of Retinoblastoma in the hub causes hub cell division and conversion to CySCs. • Retinoblastoma acts through E2F to maintain hub quiescence, fate, and niche number. • Extended loss causes ectopic niche formation through fission of the original hub. • Overexpression of Esg or E-cadherin can suppress ectopic niche formation. 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. [ABSTRACT FROM AUTHOR]