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Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells
Chengcheng Song1; Faxiang Xu1; Zhili Ren1; Yumeng Zhang1; Ya Meng1,5; Yiqi Yang2; Shreyas Lingadahalli2; Edwin Cheung2; Gang Li2; Weiwei Liu1,3; Jianbo Wan4; Yang Zhao6; Guokai Chen1,3
2019-08
Source PublicationSTEM CELL REPORTS
ISSN2213-6711
Volume13Issue:2Pages:338-351
Other Abstract

Pyruvate is a key metabolite in glycolysis and the tricarboxylic acid (TCA) cycle. Exogenous pyruvate modulates metabolism, provides cellular protection, and is essential for the maintenance of human preimplantation embryos and human embryonic stem cells (hESCs). However, little is known about how pyruvate contributes to cell-fate determination during epiblast stage. In this study, we used hESCs as a model to demonstrate that elevated exogenous pyruvate shifts metabolic balance toward oxidative phosphorylation in both maintenance and differentiation conditions. During differentiation, pyruvate potentiates mesoderm and endoderm lineage specification. Pyruvate production and its mitochondrial metabolism are required in BMP4-induced mesoderm differentiation. However, the TCA-cycle metabolites do not have the same effect as pyruvate on differentiation. Further study shows that pyruvate increases AMP/ATP ratio, activates AMPK, and modulates the mTOR pathway to enhance mesoderm differentiation. This study reveals that exogenous pyruvate not only controls metabolism but also modulates signaling pathways in hESC differentiation.

KeywordHescs Pyruvate Bmp4 Glycolysis Tca Cycle Ampk Wnt Metabolism Mesoderm Differentiation
DOI10.1016/j.stemcr.2019.06.003
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell & Tissue Engineering ; Cell Biology
WOS IDWOS:000481410000009
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Chinese Medical Sciences
Affiliation1.Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau, China
2.Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, China
3.Bioimaging and Stem Cell Core Facility, Faculty of Health Sciences, University of Macau, Macau, China
4.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
5.Center of Interventional Radiology, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong 519000, China
6.The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Chengcheng Song,Faxiang Xu,Zhili Ren,et al. Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells[J]. STEM CELL REPORTS,2019,13(2):338-351.
APA Chengcheng Song.,Faxiang Xu.,Zhili Ren.,Yumeng Zhang.,Ya Meng.,...&Guokai Chen.(2019).Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells.STEM CELL REPORTS,13(2),338-351.
MLA Chengcheng Song,et al."Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells".STEM CELL REPORTS 13.2(2019):338-351.
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