| Mitochondrial Pyruvate Carrier Differentially Controls the Self-Renewal and Differentiation of Human Pluripotent Stem Cells |
| 論文作者 |
Jiang, DC; Wang, YC; Chen, YH; Tian, C; Li, X; Li, S; Gu, XS; Jiang, CP; Ding, QR |
| 期刊/會(huì)議名稱 |
JOURNAL OF CELLULAR PHYSIOLOGY |
| 論文年度 |
2025 |
| 論文類別 |
|
| 摘要 |
Mitochondria are crucial for cell fate determination, yet their roles in human pluripotent stem cell (hPSC) fate changes have remained underexplored. Here, we designed a CRISPR library targeting 661 mitochondrial proteins and identified the MPC (mitochondrial pyruvate carrier) as a critical regulator of hPSC self-renewal and pluripotency. Notably, MPC inhibition reduced hPSC self-renewal and endoderm differentiation while promoting mesoderm differentiation, with no effect on ectoderm differentiation, all mediated by influencing glycolytic acetyl-CoA production. Specifically, the decrease in acetyl-CoA following MPC inhibition affected histone acetylation in hPSCs, compromising self-renewal. In contrast, MPC inhibition did not impact histone acetylation in differentiated cells; instead, it reduced the acetylation of non-histone proteins-EP300 and SMAD2-thereby enhancing mesoderm differentiation and repressing endoderm differentiation, respectively. These findings suggest that distinct effector proteins respond to variations in acetyl-CoA levels at different developmental stages, leading to a context-dependent regulation of cell fate determination by glycolytic acetyl-CoA in hPSCs. |
| 卷 |
240 |
| 影響因子 |
4 |
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