Journal
CELL STEM CELL
Volume 26, Issue 4, Pages 558-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2020.01.018
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Funding
- UW-Madison flow cytometry core [P30 CA014520, 1S10RR025483-01]
- NIH T32 [T32GM008688, T32AG000213]
- SciMed graduate research fellowship
- AFAR Young Investigator Award
- Sloan Foundation fellowship
- DP2 NIH New Innovator Award
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Maintaining a healthy proteome throughout life is critical for proper somatic stem cell function, but the complexities of the stem cell response to increases in damaged or aggregated proteins remain unclear. Here we demonstrate that adult neural stem cells (NSCs) utilize aggresomes to recover from disrupted proteostasis and describe a novel function for the intermediate filament vimentin in proteostasis as a spatial coordinator of proteasomes to the aggresome. In the absence of vimentin, NSCs have a reduced capacity to exit quiescence, a time when NSCs are required to clear a wave of aggregated proteins, and demonstrate an early agedependent decline in proliferation and neurogenesis. Taken together, these data reveal a significant role of vimentin and aggresomes in the regulation of proteostasis during quiescent NSC activation.
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