The KAP1 chromatin regulator and Paupar long non-coding RNA control subventricular zone neural stem cell maintenance and neurogenesis

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.