The transcriptional co-activator Yap1 promotes adult hippocampal neural stem cell activation

Fan W, Jurado-Arjona J, Alanis-Lobato G, Péron S, Berger C, Andrade-Navarro MA, Falk S, Berninger B (2023)

Publication Type: Journal article

Publication year: 2023

Journal

EMBO Journal EMBO Press

DOI: 10.15252/embj.2021110384

Abstract

Most adult hippocampal neural stem cells (NSCs) remain quiescent, with only a minor portion undergoing active proliferation and neurogenesis. The molecular mechanisms that trigger the transition from quiescence to activation are still poorly understood. Here, we found the activity of the transcriptional co-activator Yap1 to be enriched in active NSCs. Genetic deletion of Yap1 led to a significant reduction in the relative proportion of active NSCs, supporting a physiological role of Yap1 in regulating the transition from quiescence to activation. Overexpression of wild-type Yap1 in adult NSCs did not induce NSC activation, suggesting tight upstream control mechanisms, but overexpression of a gain-of-function mutant (Yap1-5SA) elicited cell cycle entry in NSCs and hilar astrocytes. Consistent with a role of Yap1 in NSC activation, single cell RNA sequencing revealed a partial induction of an activated NSC gene expression program. Furthermore, Yap1-5SA expression also induced expression of Taz and other key components of the Yap/Taz regulon that were previously identified in glioblastoma stem cell-like cells. Consequently, dysregulated Yap1 activity led to repression of hippocampal neurogenesis, aberrant cell differentiation, and partial acquisition of a glioblastoma stem cell-like signature.

Authors with CRIS profile

Sven Falk Lehrstuhl für Biochemie und Pathobiochemie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

E032: Identifying molecular nexuses in microtubule-associated neurodevelopmental diseases July 1, 2023 - Dec. 31, 2025

Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE)

How to cite

APA:

Fan, W., Jurado-Arjona, J., Alanis-Lobato, G., Péron, S., Berger, C., Andrade-Navarro, M.A.,... Berninger, B. (2023). The transcriptional co-activator Yap1 promotes adult hippocampal neural stem cell activation. EMBO Journal. https://doi.org/10.15252/embj.2021110384

MLA:

Fan, Wenqiang, et al. "The transcriptional co-activator Yap1 promotes adult hippocampal neural stem cell activation." EMBO Journal (2023).

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