Title: The spatio-temporal regulation of neural stem cells by their progeny
Abstract: Life-long maintenance of stem cells implies that feedback mechanisms from the niche regulate their quiescence/activation dynamics. Using mouse adult subventricular neural stem cell (NSC) niche as a model system, I will discuss our recent finding showing how NSCs interact with distinct niche cell types and how beating of ependymal cells cilia affects their quiescent/activation dynamics. We charted a precise spatiotemporal map of functional responses in NSCs induced by multiple niche cells and used machine learning to predict NSC interactions with specific niche cell types. We further revealed a feedback mechanism whereby NSC proliferative state is directly repressed by transient amplifying cells (TAPs), their rapidly dividing progeny. NSC processes wrap around TAPs and display hot-spots of Ca2+ activity at their points of contact, mediated by ephrin signaling. The modulation of ephrin signaling or ablation of progeny altered the Ca2+ signature of NSCs leading to their activation.
We also showed that mechanical forces created by the beating of cilia of ependymal cells sustain NSCs quiescent state, while arrest of cilia beating and/or CRISPR-Cas9 deletion of mechanoreceptors from NSCs triggers their activation through Ca2+ signaling. In vivo pharmacological activation of mechanosensitive receptors enriched in NSCs reverts their transition to proliferation induced by cilia beating arrest, highlighting an exquisite link between mechanical forces created by ependymal cilia beating and NSC activation.
Our Seminar Lab Series will be offered in hybrid format:
The in-person seminar is each Tuesday during the semester from noon-1 p.m. at the Discovery Building, DeLuca Forum.
To join online, please click the zoom link below:
https://uwmadison.zoom.us/j/96958883460
*if you are asked for a passcode: 970506