在人类多能干细胞的中胚层细胞命运分化过程中,培养基酸中毒驱动了心脏分化。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI:10.1016/j.stemcr.2024.07.012
Weiwei Liu, Hsun-Ting Hsieh, Ziqing He, Xia Xiao, Chengcheng Song, En Xin Lee, Ji Dong, Chon Lok Lei, Jiaxian Wang, Guokai Chen
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引用次数: 0

摘要

要发挥人类多能干细胞(hPSCs)的巨大潜力,有效的系特异性分化至关重要。在本报告中,我们研究了培养基pH值的调节和相关代谢变化如何影响hPSCs的中胚层分化。我们发现,在没有外源诱导剂的情况下,培养基pH值的日常波动对细胞命运的异质性至关重要。在没有其他信号调节剂的情况下,仅酸性环境就能导致心肌细胞的生成。相反,即使存在传统的心脏诱导剂,培养基碱化也会抑制心脏命运。我们随后证明,酸性环境抑制糖酵解以促进心脏分化,而碱性条件促进糖酵解并使分化转向其他细胞类型。我们还进一步证明,抑制糖酵解或激活 AMPK 可以挽救碱化条件下的心脏分化,而单独抑制糖酵解可以驱动心脏细胞的命运。这项研究强调,pH 值变化可重塑代谢模式并调节信号通路,从而控制细胞命运。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Medium acidosis drives cardiac differentiation during mesendoderm cell fate specification from human pluripotent stem cells.

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.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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