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乳酸激活小鼠胚胎干细胞中的生殖系和卵裂胚胎基因。

Lactate Activates Germline and Cleavage Embryo Genes in Mouse Embryonic Stem Cells.

机构信息

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Cells. 2022 Feb 4;11(3):548. doi: 10.3390/cells11030548.

DOI:10.3390/cells11030548
PMID:35159357
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8833948/
Abstract

Lactate was recently found to mediate histone lysine lactylation and facilitate polarization of M1 macrophages, indicating its role in metabolic regulation of gene expression. During somatic cell reprogramming, lactate promotes histone lactylation of pluripotency genes and improves reprogramming efficiency. However, the function of lactate in cell fate control in embryonic stem cells (ESCs) remains elusive. In this study, we revealed that lactate supplementation activated germline genes in mouse ESCs. Lactate also induced global upregulation of cleavage embryo genes, such as members of the gene family. Further exploration demonstrated that lactate stimulated H3K18 lactylation accumulation on germline and cleavage embryo genes, which in turn promoted transcriptional elongation. Our findings indicated that lactate supplementation expanded the transcriptional network in mouse ESCs.

摘要

最近发现,乳酸可介导组蛋白赖氨酸乳酸化,促进 M1 巨噬细胞极化,提示其在基因表达的代谢调控中发挥作用。在体细胞重编程过程中,乳酸促进多能性基因的组蛋白乳酸化,提高重编程效率。然而,乳酸在胚胎干细胞(ESCs)中对细胞命运控制的功能仍不清楚。在这项研究中,我们揭示了补充乳酸可激活小鼠 ESCs 中的种系基因。乳酸还诱导了胚胎基因的全面上调,如基因家族的成员。进一步的探索表明,乳酸刺激种系和胚胎基因上 H3K18 乳酸化的积累,从而促进转录延伸。我们的研究结果表明,补充乳酸可扩展小鼠 ESCs 中的转录网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/ef2e8f23a271/cells-11-00548-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/69438de45ee0/cells-11-00548-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/1be64acdc1c1/cells-11-00548-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/4383a507d4a5/cells-11-00548-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/ef2e8f23a271/cells-11-00548-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/69438de45ee0/cells-11-00548-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/6a9e5ce8a2af/cells-11-00548-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/1be64acdc1c1/cells-11-00548-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/4383a507d4a5/cells-11-00548-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5e6/8833948/ef2e8f23a271/cells-11-00548-g005.jpg

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Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition.
乳酸通过AKT-PKM2轴抑制小鼠胚胎腭间充质细胞软骨形成。
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Lactylation-Driven NUPR1 Promotes Immunosuppression of Tumor-Infiltrating Macrophages in Hepatocellular Carcinoma.乳酰化驱动的NUPR1促进肝细胞癌中肿瘤浸润巨噬细胞的免疫抑制
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