生物
细胞生物学
干细胞
线粒体
PI3K/AKT/mTOR通路
造血
造血干细胞
TSC1
雷帕霉素的作用靶点
TSC2
信号转导
作者
Yukai Lu,Zihao Zhang,Song Wang,Yan Qi,Fang Chen,Yu Xu,Mingqiang Shen,Mo Chen,Naicheng Chen,Lijing Yang,Shilei Chen,Fengchao Wang,Yongping Su,Mengjia Hu,Junping Wang
标识
DOI:10.1016/j.stemcr.2022.01.011
摘要
Mitochondria are fundamental but complex determinants for hematopoietic stem cell (HSC) maintenance. However, the factors involved in the regulation of mitochondrial metabolism in HSCs and the underlying mechanisms have not been fully elucidated. Here, we identify sterol regulatory element binding factor-1c (Srebf1c) as a key factor in maintaining HSC biology under both steady-state and stress conditions. Srebf1c knockout (Srebf1c-/-) mice display increased phenotypic HSCs and less HSC quiescence. In addition, Srebf1c deletion compromises the function and survival of HSCs in competitive transplantation or following chemotherapy and irradiation. Mechanistically, SREBF1c restrains the excessive activation of mammalian target of rapamycin (mTOR) signaling and mitochondrial metabolism in HSCs by regulating the expression of tuberous sclerosis complex 1 (Tsc1). Our study demonstrates that Srebf1c plays an important role in regulating HSC fate via the TSC1-mTOR-mitochondria axis.
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