Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration
| Autor: | Xiao Yan, Heather A. Himburg, Katherine Pohl, Mamle Quarmyne, Evelyn Tran, Yurun Zhang, Tiancheng Fang, Jenny Kan, Nelson J. Chao, Liman Zhao, Phuong L. Doan, John P. Chute |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Cell Reports, Vol 17, Iss 6, Pp 1584-1594 (2016) |
| Druh dokumentu: | article |
| ISSN: | 2211-1247 93607105 |
| DOI: | 10.1016/j.celrep.2016.10.025 |
| Popis: | 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 (Grb10m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10+/+ mice. After total body irradiation (TBI), Grb10m/+ 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. |
| Databáze: | Directory of Open Access Journals |
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