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The transcription factor ZEB1 regulates stem cell self-renewal and cell fate in the adult hippocampus

Gupta, Bhavana, Errington, Adam C., Jimenez-Pascual, Ana, Eftychidis, Vasileios, Brabletz, Simone, Stemmler, Marc P., Brabletz, Thomas, Petrik, David and Siebzehnrubl, Florian A. 2021. The transcription factor ZEB1 regulates stem cell self-renewal and cell fate in the adult hippocampus. Cell Reports 36 (8) , 109588. 10.1016/j.celrep.2021.109588

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Abstract

Radial glia-like (RGL) stem cells persist in the adult mammalian hippocampus, where they generate new neurons and astrocytes throughout life. The process of adult neurogenesis is well documented, but cellautonomous factors regulating neuronal and astroglial differentiation are incompletely understood. Here, we evaluate the functions of the transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) in adult hippocampal RGL cells using a conditional-inducible mouse model. We find that ZEB1 is necessary for self-renewal of active RGL cells. Genetic deletion of Zeb1 causes a shift toward symmetric cell division that consumes the RGL cell and generates pro-neuronal progenies, resulting in an increase of newborn neurons and a decrease of newly generated astrocytes. We identify ZEB1 as positive regulator of the ets-domain transcription factor ETV5 that is critical for asymmetric division

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: Cell Press
ISSN: 2211-1247
Funders: MRC
Date of First Compliant Deposit: 16 September 2021
Date of Acceptance: 30 July 2021
Last Modified: 28 Feb 2022 11:12
URI: https://orca.cardiff.ac.uk/id/eprint/144180

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