Darcie Moore, PhD – Slide of the Week

Darcie Moore Slide of the Week

Title: The intermediate filament vimentin enhances quiescence exit in neural stem cells

Legend:  Vimentin enhances neural stem cell (NSC) proliferation with aging through assisting in aggresome-mediated protein turnover. A) Representative division of a vimentin-mNeon neural stem cell during quiescence exit in vitro. B-C) 7 weeks (wks) or 5 months (mos) old WT and vimentin knock out (KO) mice were injected with 50 mg/kg EdU once per day for 4 days, sacrificed 1 day following the last EdU injection and then analyzed for proliferative (EdU+) NSCs in the subgranular zone. (n≥6; Two-way ANOVA with post-hoc Tukey’s test; mean ± SD). Scale bars, 10 µm (A), 50 µm (B). **p<0.001, ****p<0.0001. Nuclei are labeled with DAPI.

Citation: Morrow, C.S., Porter, T., Xu, N., Arndt, Z., Ako-Asare, K., Heo, H., Thompson, E., Moore, DL. (2020)
Vimentin-mediated proteasome localization to the aggresome in neural stem cells enhances
quiescence exit. Cell Stem Cell.

Abstract:  Neurogenesis is thought to be sustained throughout life through the constant regulation of neural stem cell (NSC) quiescence exit, a time in which a NSC enters the cell cycle to generate more neural stem cells and/or other neural cell types. One critical component of NSC quiescence exit is the clearance of aggregated proteins. However, the coordinated mechanisms by which these proteins are cleared are largely unknown. Here we show that neural stem cells utilize aggresomes, organized protein degradation centers located at the centrosome within a vimentin cage, during quiescence exit and that a lack of vimentin around the aggresome impairs protein turnover and NSC proliferation in vivo during aging. These findings describe a mechanism for the maintenance of proteostasis in neural stem cells with implications for other stem cell niches throughout the body in a variety of contexts.

About the Lab: The Moore Lab is interested in understanding the mechanisms that neural stem cells (NSCs) utilize to stay active during aging. More specifically, the Moore Lab is interested in understanding how NSCs utilize asymmetric cell division to maintain a pristine proteome and preserve cellular function.

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