Cell-cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Authors: Diego Sainz de la Maza, Silvana Hof-Michel, Lee Phillimore, Christian Bökel, Marc Amoyel

Institutions:

• Department of Cell and Developmental Biology, University College London, UK
• Department of Developmental Genetics, Philipps University Marburg, Germany

Publication: Cell

Date: May, 2022

Link: Cell-cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Abstract:

Whereas stem and progenitor cells proliferate to maintain tissue homeostasis, fully differentiated cells exit the cell cycle. How cell identity and cell-cycle state are coordinated during differentiation is still poorly understood. The Drosophila testis niche supports germline stem cells and somatic cyst stem cells (CySCs). CySCs give rise to post-mitotic cyst cells, providing a tractable model to study the links between stem cell identity and proliferation. We show that, while cell-cycle progression is required for CySC self-renewal, the E2f1/Dp transcription factor is dispensable for self-renewal but instead must be silenced by the Drosophila retinoblastoma homolog, Rbf, to permit differentiation. Continued E2f1/Dp activity inhibits the expression of genes important for mitochondrial activity. Furthermore, promoting mitochondrial biogenesis rescues the differentiation of CySCs with ectopic E2f1/Dp activity but not their cell-cycle exit. In sum, E2f1/Dp coordinates cell-cycle progression with stem cell identity by regulating the metabolic state of CySCs.