乳酸通过组蛋白乳酸化修饰调节红细胞祖细胞的分化

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-09 DOI:10.1016/j.isci.2025.112842

Qianqian Yang , Hengchao Zhang , Yan Hou , Shaoyang Gu , Lixiang Chen , Fumin Xue , Xiuyun Wu

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引用次数: 0

摘要

乳酸通过调节代谢稳态和组蛋白乳酸化，在多种生物事件中起着重要的调节作用。然而，乳酸和组蛋白乳酸化在人红细胞生成中的作用尚不清楚。在这里，我们通过添加糖酵解抑制剂2-脱氧-d-葡萄糖（2-DG）或外源性乳酸Na-La来降低或增加细胞内乳酸水平，探索乳酸在红细胞生成中的作用。结果表明，糖酵解抑制可促进红系祖细胞分化，阻断细胞周期，减少集落形成单位-红系（CFU-E）的集落形成，而乳酸水平升高可延缓红系祖细胞分化，促进CFU-E集落形成。我们还发现乳酸水平直接调节H3K14la强度。此外，我们还发现与干细胞多能性和分化相关的细胞周期和分裂相关基因CCNB1、CFL1、CENPA和GNAI2的H3K14la丰度和基因表达发生了变化。总之，我们的研究表明乳酸通过组蛋白乳酸化调节基因表达影响早期红系祖细胞的分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification

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Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification

Lactate plays important regulatory roles in a variety of biological events by regulating metabolic homeostasis and histone lactylation. However, the role of lactate and histone lactylation in human erythropoiesis remains unclear. Here, we explored the role of lactate in erythropoiesis by adding the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) or exogenous lactate Na-La to decrease or increase intracellular lactate levels. The results showed the inhibition of glycolysis promoted erythroid progenitors’ differentiation, blocked cell cycle, and reduced colony formation of colony-forming unit-erythroid (CFU-E), whereas elevated lactate levels delayed erythroid progenitors’ differentiation and promoted CFU-E colony formation. We also found lactate levels directly regulated H3K14la intensity. Furthermore, we showed changes in H3K14la abundance and gene expression of the cell cycle and division-related genes CCNB1, CFL1, CENPA, and GNAI2, which were associated with stem cell pluripotency and differentiation. In conclusion, our study reveals lactate affects cell differentiation of early erythroid progenitors by regulating gene expression through histone lactylation.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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