Medium acidosis drives cardiac differentiation during mesendoderm cell fate specification from human pluripotent stem cells.

Autor:	Liu W; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China; Biological Imaging and Stem Cell Core Facility, Faculty of Health Sciences, University of Macau, Macau SAR, China. Electronic address: weiweiliu@um.edu.mo., Hsieh HT; Biological Imaging and Stem Cell Core Facility, Faculty of Health Sciences, University of Macau, Macau SAR, China., He Z; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China; GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China., Xiao X; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China., Song C; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China., Lee EX; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China., Dong J; GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China., Lei CL; Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, China., Wang J; HELP Stem Cell Innovations Ltd. Co., Nanjing, Jiangsu, China., Chen G; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China; MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, China. Electronic address: guokaichen@um.edu.mo.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2024 Sep 10; Vol. 19 (9), pp. 1304-1319. Date of Electronic Publication: 2024 Aug 22.
DOI:	10.1016/j.stemcr.2024.07.012
Abstrakt:	Effective lineage-specific differentiation is essential to fulfilling the great potentials of human pluripotent stem cells (hPSCs). In this report, we investigate how modulation of medium pH and associated metabolic changes influence mesendoderm differentiation from hPSCs. We show that daily medium pH fluctuations are critical for the heterogeneity of cell fates in the absence of exogenous inducers. Acidic environment alone leads to cardiomyocyte generation without other signaling modulators. In contrast, medium alkalinization is inhibitory to cardiac fate even in the presence of classic cardiac inducers. We then demonstrate that acidic environment suppresses glycolysis to facilitate cardiac differentiation, while alkaline condition promotes glycolysis and diverts the differentiation toward other cell types. We further show that glycolysis inhibition or AMPK activation can rescue cardiac differentiation under alkalinization, and glycolysis inhibition alone can drive cardiac cell fate. This study highlights that pH changes remodel metabolic patterns and modulate signaling pathways to control cell fate. Competing Interests: Declaration of interests W.L. and G.C. filed a patent application based on cardiomyocyte differentiation that is induced by acidic pH. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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