PMID- 35500439
OWN - NLM
STAT- MEDLINE
DCOM- 20220530
LR  - 20220601
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 612
DP  - 2022 Jul 5
TI  - The functional role of OGDH for maintaining mitochondrial respiration and 
      identity of primed human embryonic stem cells.
PG  - 30-36
LID - S0006-291X(22)00582-4 [pii]
LID - 10.1016/j.bbrc.2022.04.059 [doi]
AB  - Human embryonic stem cells (hESCs) can self-renew infinitely and differentiate 
      into the cell types of all lineages of our body, holding great promise for 
      investigating early human embryo development and providing functional cells for 
      disease treatment. For the full application of hESCs, it is necessary to 
      elucidate how hESCs maintain their identity. Recent studies have shown that 
      glycolysis and mitochondrial respiration are linked to pluripotency states. 
      However, the function of mitochondrial respiration in hESCs has not been fully 
      understood. Herein, we report that the adenosine triphosphate (ATP) production 
      rate is comparable between mitochondrial respiration and glycolysis, suggesting 
      an important contribution of mitochondrial respiration to ATP production in 
      conventionally cultured hESCs. To investigate the function of mitochondrial 
      respiration, we silence OGDH expression in hESCs by the inducible CRISPRi method, 
      and find that OGDH knockdown (KD) results in disrupted TCA (tricarboxylic acid) 
      cycle, and diminished mitochondrial respiration activity and total ATP level. 
      Moreover, OGDH KD leads to hESC death and aberrant transcriptional program. 
      Interestingly, blockage of the electron transport chain (ETC) by small molecule 
      inhibitors gives rise to the phenotype similar to that observed in OGDH deficient 
      hESCs. Therefore, genetic and pharmacological perturbations of the mitochondrial 
      respiration impair identity of hESCs. Collectively, our study highlights the 
      pivotal role of the mitochondrial respiration activity for the stemness 
      maintenance of primed hESCs, and unveils OGDH as a key regulator for the proper 
      production of ATP and TCA cycle metabolites in primed hESCs.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Liu, Yujie
AU  - Liu Y
AD  - Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key 
      Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Wang, Han
AU  - Wang H
AD  - Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key 
      Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Shao, Min
AU  - Shao M
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, CAS Center for Excellence in Molecular Cell Science, 
      University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 
      China.
FAU - Jin, Ying
AU  - Jin Y
AD  - Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key 
      Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China; CAS Key Laboratory of Tissue Microenvironment and 
      Tumor, Shanghai Institute of Nutrition and Health, CAS Center for Excellence in 
      Molecular Cell Science, University of Chinese Academy of Sciences, Chinese 
      Academy of Sciences, Shanghai, China; Basic Clinical Research Center, Ren Ji 
      Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 
      Electronic address: yjin@sibs.ac.cn.
FAU - Liao, Bing
AU  - Liao B
AD  - Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key 
      Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China; Basic Clinical Research Center, Ren Ji Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic 
      address: bingliao@shsmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220415
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Cell Differentiation/genetics
MH  - Embryo, Mammalian
MH  - *Human Embryonic Stem Cells/metabolism
MH  - Humans
MH  - Respiration
OTO - NOTNLM
OT  - ATP production
OT  - Human embryonic stem cells
OT  - Mitochondrial respiration
OT  - OGDH
OT  - Primed pluripotency
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/05/03 06:00
MHDA- 2022/05/31 06:00
CRDT- 2022/05/02 18:23
PHST- 2022/02/18 00:00 [received]
PHST- 2022/04/13 00:00 [accepted]
PHST- 2022/05/03 06:00 [pubmed]
PHST- 2022/05/31 06:00 [medline]
PHST- 2022/05/02 18:23 [entrez]
AID - S0006-291X(22)00582-4 [pii]
AID - 10.1016/j.bbrc.2022.04.059 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2022 Jul 5;612:30-36. doi: 
      10.1016/j.bbrc.2022.04.059. Epub 2022 Apr 15.