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

Sainz de la Maza, Diego; Hof-Michel, Silvana; Phillimore, Lee; Bökel, Christian; Amoyel, Marc; (2022) Cell-cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis. Cell Reports , 39 (6) , Article 110774. 10.1016/j.celrep.2022.110774. Green open access

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Abstract

Summary 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.

Type: Article
Title: Cell-cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2022.110774
Publisher version: https://doi.org/10.1016/j.celrep.2022.110774
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10148616
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