|
Status |
Public on Nov 01, 2022 |
Title |
Rb family proteins are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
The long-term maintenance of the adult neurogenic niche and neurogenesis is dependent on the proper regulation of entry and exit from quiescence. The dynamic transition from quiescence to activation is a complex process requiring not only precise cell cycle control, but also a co-ordinated phenotypic transition involving transcriptional and morphological changes. Presently, the mechanisms by which such a complex repertoire of factors interact and co-ordinate with the core cell cycle machinery to mediate these critical NSC fate transitions remains unknown. Here we show that the Rb/E2F axis functions as an on-off switch for NSC quiescence and activation, by linking the cell cycle machinery to pivotal regulators of NSC fate. Compound deletion of Rb family proteins results in massive activation and expansion of NSCs, and induces a global transcriptomic transition towards NSC activation followed by niche depletion. Deletion of their target activator E2Fs1/3 results in the failure of NSCs to become activated and the acquisition of a global transcriptome associated with intractable NSC quiescence and the cessation of adult neurogenesis. We further show that the Rb/E2F axis orchestrates these fate transitions through the direct regulation of factors essential to NSC function, including REST and ASCL1. This places the Rb/E2F axis as a master regulator of NSC fate, coordinating cell cycle control with NSC activation and quiescence fate transitions.
|
|
|
Overall design |
Six samples total; three biological replicates were analyzed for each of two conditions (two genotypes; three replicates per genotype)
|
|
|
Contributor(s) |
Fong BC, Slack RS |
Citation(s) |
- Fong BC, Chakroun I, Iqbal MA, Paul S et al. The Rb/E2F axis is a key regulator of the molecular signatures instructing the quiescent and activated adult neural stem cell state. Cell Rep 2022 Nov 1;41(5):111578. PMID: 36323247
|
|
Submission date |
Dec 13, 2021 |
Last update date |
Nov 03, 2022 |
Contact name |
Ruth S Slack |
Organization name |
University of Ottawa
|
Department |
Brain and Mind Research Institute
|
Lab |
Ruth Slack Laboratory
|
Street address |
451 Smyth Rd
|
City |
Ottawa |
State/province |
ON |
ZIP/Postal code |
K1H8M5 |
Country |
Canada |
|
|
Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
Samples (6)
|
|
This SubSeries is part of SuperSeries: |
GSE190766 |
Rb family proteins and Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state |
|
Relations |
BioProject |
PRJNA788447 |