Residential College | false |
Status | 已發表Published |
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 Publication | STEM CELL REPORTS |
ISSN | 2213-6711 |
Volume | 13Issue: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. |
Keyword | Hescs Pyruvate Bmp4 Glycolysis Tca Cycle Ampk Wnt Metabolism Mesoderm Differentiation |
DOI | 10.1016/j.stemcr.2019.06.003 |
Indexed By | SCIE |
Language | 英語English |
WOS Research Area | Cell Biology |
WOS Subject | Cell & Tissue Engineering ; Cell Biology |
WOS ID | WOS:000481410000009 |
Scopus ID | 2-s2.0-85070210742 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Faculty of Health Sciences Institute of Chinese Medical Sciences |
Corresponding Author | Guokai Chen |
Affiliation | 1.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 Affilication | Centre of Reproduction, Development and Aging |
Corresponding Author Affilication | Centre of Reproduction, Development and Aging; Faculty 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,Yiqi Yang,Shreyas Lingadahalli,Edwin Cheung,Gang Li,Weiwei Liu,Jianbo Wan,Yang Zhao,&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. |
Files in This Item: | There are no files associated with this item. |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment