Srebf1c preserves hematopoietic stem cell function and survival as a switch of mitochondrial metabolism
Yukai Lu, Zihao Zhang, Song Wang, Yan Qi, Fang Chen, Yang Xu, Mingqiang Shen, Mo Chen, Naicheng Chen, Lijing Yang, Shilei Chen, Fengchao Wang, Yongping Su, Mengjia Hu, Junping Wang
Abstract
) 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.
Topics & Concepts
BiologyHaematopoiesisFunction (biology)Stem cellCell survivalCell biologyHematopoietic stem cellMitochondrionCell metabolismMetabolismCellGeneticsComputational biologyApoptosisBiochemistryEpigenetics and DNA MethylationHematopoietic Stem Cell TransplantationCancer, Hypoxia, and Metabolism