期刊
CELL REPORTS
卷 17, 期 6, 页码 1584-1594出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.10.025
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资金
- National Institute of Allergy and Infectious Diseases (NIAID) [AI067769]
- National Heart, Lung, and Blood Institute (NHLBI) [HL086998]
- California Institute for Regenerative Medicine Leadership Award [LA1-08014]
Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10(m/+) mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10(+/+) mice. After total body irradiation (TBI), Grb10(m/+) mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution, as compared to Grb10(+/+) mice. Grb10-deficient HSCs displayed increased proliferation after competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10-deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene Grb10 in regulating HSC self-renewal and regeneration and suggests that the inhibition of Grb10 can promote hematopoietic regeneration in vivo.
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