E-resources
Peer reviewed
Open access
-
Fan, Wenqiang; Jurado‐Arjona, Jerónimo; Alanis‐Lobato, Gregorio; Péron, Sophie; Berger, Christian; Andrade‐Navarro, Miguel A; Falk, Sven; Berninger, Benedikt
EMBO journal, 01 June 2023, Volume: 42, Issue: 11Journal Article
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. Synopsis In the adult hippocampus, most neural stem cells are quiescent and only few become activated and generate new neurons. This study demonstrates an important role of the transcriptional activator Yap1 in mediating the transition between quiescence and activation. Yap1 activity is enriched in activated neural stem cells. Loss‐of‐function and gain‐of‐function experiments support that Yap1 promotes neural stem cell activation. Prolonged Yap1 gain‐of‐function represses hippocampal neurogenesis. Prolonged Yap1 activation leads to aberrant neural cell differentiation and partial glioblastoma stem cell‐like signature. The Hippo pathway effector protein Yap1 mediates the transition between quiescence and activation in adult hippocampal neural stem cells.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.