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

转录因子 ZEB1 调节成年海马中的干细胞自我更新和细胞命运

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作者:Bhavana Gupta, Adam C Errington, Ana Jimenez-Pascual, Vasileios Eftychidis, Simone Brabletz, Marc P Stemmler, Thomas Brabletz, David Petrik, Florian A Siebzehnrubl

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 cell-autonomous 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.

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