Affiliation:
1. Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China
2. Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA
3. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China
Abstract
Abstract
Human embryonic stem cells (hESCs) depend on glycolysis for energy supply and pluripotency and switch to oxidative phosphorylation upon differentiation. The underlying mechanisms remain unclear. Here, we demonstrate that indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in primed hESCs and its expression rapidly downregulated upon hESC differentiation. IDO1 is required to maintain pluripotency by suppressing mitochondria activity and promoting glycolysis through the increase of NAD+/NADH ratio. The upregulation of IDO1 during hESC differentiation suppresses the differentiation of hESCs into certain lineages of cells such as cardiomyocytes, which depend on oxidative phosphorylation to satisfy their high energy demand. Therefore, IDO1 plays important roles in maintaining the pluripotency of hESCs. Stem Cells 2019;37:1158–1165
Funder
California Institute for Regenerative Medicine
Shenzhen “Sanming” Project of Medicine
Development and Reform Commission of Shenzhen Municipality
Natural Science Foundation of Guangdong Province
Guangdong Provincial Key Laboratory of Cancer Immunotherapy
Key Research and Development Program of Guangdong Province
National High-Tech R&D Program
Leading Talents of Guangdong Province Program
National Natural Science Foundation of China
National High-tech Research and Development Program
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Developmental Biology,Molecular Medicine
Cited by
9 articles.
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