PT  - JOURNAL ARTICLE
AU  - Albina Ibrayeva
AU  - Maxwell Bay
AU  - Elbert Pu
AU  - David Jörg
AU  - Lei Peng
AU  - Heechul Jun
AU  - Naibo Zhang
AU  - Daniel Aaron
AU  - Congrui Lin
AU  - Galen Resler
AU  - Mi-Hyeon Jang
AU  - Benjamin D. Simons
AU  - Michael A. Bonaguidi
TI  - Early Stem Cell Aging in the Mature Brain
AID  - 10.1101/654608
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 654608
4099  - http://biorxiv.org/content/early/2019/06/20/654608.short
4100  - http://biorxiv.org/content/early/2019/06/20/654608.full
AB  - Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initiate stem cell dysfunction represent early targets to enhance tissue resiliency throughout life. Here, we pinpoint multiple factors that compromise neural stem cell (NSC) behavior in the adult hippocampus. We find that NSCs exhibit asynchronous depletion by identifying short-term (ST-NSC) and intermediate-term NSCs (IT-NSCs). ST-NSC divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent IT-NSCs are maintained for months, but are pushed out of homeostasis by lengthening quiescence. Single cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of cellular aging in the mature brain, including changes in tyrosine-protein kinases Abl1 and Abl2. Treatment with the Abl-inhibitor Imatinib was sufficient to overcome deep quiescence and restore NSC proliferation in the middle-aged brain. Further examination of mature NSC with old epidermal, hematopoietic and muscle stem cell transcriptomes identified consensus changes in stem cell aging. Our study elucidates multiple origins of adult neurogenesis decline and reveals that hippocampal NSCs are particularly vulnerable to a shared stem cell aging signature.