Abstract
Neural stem cells (NSCs) in the subventricular zone (SVZ) produce neurons throughout life. However, the epigenetic mechanisms that maintain NSCs and control neurogenesis remain unclear. We previously showed the long non-coding RNA (lncRNA) Paupar and KAP1 transcription co-factor control neuroblastoma cell growth. In the last stages of olfactory bulb (OB) neurogenesis, these two molecules affect rates of neurogenesis. Here we investigated upstream functions with inducible knockout and in vivo knockdown electroporation and molecular analysis. KAP1 and Paupar are expressed in the SVZ, physically interact in SVZ cells, and regulate NSC behavior. KAP1 directly maintains the NSC pool and regulates the expression of genes involved in the cell cycle. Paupar, in turn, maintains stem cell quiescence by restricting lineage progression from stem cells to transit amplifying progenitors (TAPs). These results suggest important roles for KAP1 and Paupar in the control of SVZ NSC maintenance and SVZ-OB neurogenesis.
| Original language | English |
|---|---|
| Article number | 102630 |
| Journal | Stem Cell Reports |
| Volume | 20 |
| Issue number | 9 |
| Early online date | 9 Sept 2025 |
| DOIs | |
| Publication status | Published - 9 Sept 2025 |
Data Availability Statement
The RNA-seq data have been deposited in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) under the following accession numbers: KAP1: GSE298169 and Paupar: GSE298964.Funding
This project has been funded by MRC/NNSFC grant to F.G.S. (MRC MR/MO10554/1) and King Abdullah International Medical Research Center (NCR22R/013/01) grant to F.A.
| Funders | Funder number |
|---|---|
| Medical Research Council |
Keywords
- adult neurogenesis
- chromatin
- epigenetics
- KAP1
- lncRNAs
- neural stem cells
- Paupar
- quiescence
- subventricular zone
- transcription
ASJC Scopus subject areas
- Biochemistry
- Genetics
- Developmental Biology
- Cell Biology