PMID- 35148846
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220716
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 17
IP  - 3
DP  - 2022 Mar 8
TI  - Srebf1c preserves hematopoietic stem cell function and survival as a switch of 
      mitochondrial metabolism.
PG  - 599-615
LID - S2213-6711(22)00055-8 [pii]
LID - 10.1016/j.stemcr.2022.01.011 [doi]
AB  - 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Lu, Yukai
AU  - Lu Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Zhang, Zihao
AU  - Zhang Z
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Wang, Song
AU  - Wang S
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Qi, Yan
AU  - Qi Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Chen, Fang
AU  - Chen F
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Xu, Yang
AU  - Xu Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Shen, Mingqiang
AU  - Shen M
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Chen, Mo
AU  - Chen M
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Chen, Naicheng
AU  - Chen N
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Yang, Lijing
AU  - Yang L
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Chen, Shilei
AU  - Chen S
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Wang, Fengchao
AU  - Wang F
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Su, Yongping
AU  - Su Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China.
FAU - Hu, Mengjia
AU  - Hu M
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China; Chinese PLA Center for Disease Control and Prevention, 
      No. 20 Dongda Street, Fengtai District, Beijing 100071, China. Electronic 
      address: weichen1111@yahoo.com.
FAU - Wang, Junping
AU  - Wang J
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Gaotanyan Street 30, 
      Chongqing 400038, China. Electronic address: wangjunp@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220210
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
RN  - 0 (Srebf1 protein, mouse)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - *Hematopoietic Stem Cells/metabolism
MH  - Mammals/metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Sirolimus/pharmacology
MH  - Sterol Regulatory Element Binding Protein 1
MH  - *TOR Serine-Threonine Kinases/metabolism
PMC - PMC9039836
OTO - NOTNLM
OT  - Srebf1c
OT  - TSC1
OT  - hematopoietic stem cell
OT  - mTOR
OT  - mitochondrial metabolism
EDAT- 2022/02/13 06:00
MHDA- 2022/05/03 06:00
PMCR- 2022/02/10
CRDT- 2022/02/12 05:26
PHST- 2021/07/10 00:00 [received]
PHST- 2022/01/13 00:00 [revised]
PHST- 2022/01/13 00:00 [accepted]
PHST- 2022/02/13 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2022/02/12 05:26 [entrez]
PHST- 2022/02/10 00:00 [pmc-release]
AID - S2213-6711(22)00055-8 [pii]
AID - 10.1016/j.stemcr.2022.01.011 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2022 Mar 8;17(3):599-615. doi: 10.1016/j.stemcr.2022.01.011. 
      Epub 2022 Feb 10.