RT Journal Article
SR Electronic
T1 Early Stem Cell Aging in the Mature Brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 654608
DO 10.1101/654608
A1 Albina Ibrayeva
A1 Maxwell Bay
A1 Elbert Pu
A1 David Jörg
A1 Lei Peng
A1 Heechul Jun
A1 Naibo Zhang
A1 Daniel Aaron
A1 Congrui Lin
A1 Galen Resler
A1 Mi-Hyeon Jang
A1 Benjamin D. Simons
A1 Michael A. Bonaguidi
YR 2019
UL http://biorxiv.org/content/early/2019/06/20/654608.abstract
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.