| 論文編號: |
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| 第一作者所在部門: |
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| 中文論文題目: |
Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation |
| 英文論文題目: |
Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation |
| 作者: |
Wei Li, Qi Long , Hao Wu, Yanshuang Zhou , Lifan Duan, Hao Yuan , Yingzhe Ding , Yile Huang , Yi Wu , Jinyu Huang, Delong Liu, Baodan Chen, Jian Zhang , Juntao Qi, Shiwei Du, Linpeng Li , Yang Liu, Zifeng Ruan, Zihuang Liu, Zichao Liu, Yifan Zhao , Jianghuan Lu, Junwei Wang, Wai-Yee Chan & Xingguo Liu. |
| 論文出處: |
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| 刊物名稱: |
Nature Communications |
| 年: |
2022 |
| 卷: |
13 |
| 期: |
1 |
| 頁: |
7414 |
| 聯係作者: |
Xingguo Liu |
| 收錄類別: |
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| 影響因子: |
17.694 |
| 摘要: |
Pluripotent stem cells hold great promise in regenerative medicine and developmental biology studies. Mitochondrial metabolites, including tricarboxylic acid (TCA) cycle intermediates, have been reported to play critical roles in pluripotency. Here we show that TCA cycle enzymes including Pdha1, Pcb, Aco2, Cs, Idh3a, Ogdh, Sdha and Mdh2 are translocated to the nucleus during somatic cell reprogramming, primed-to-naive transition and totipotency acquisition. The nuclear-localized TCA cycle enzymes Pdha1, Pcb, Aco2, Cs, Idh3a promote somatic cell reprogramming and primed-to-naive transition. In addition, nuclear-localized TCA cycle enzymes, particularly nuclear-targeted Pdha1, facilitate the 2-cell program in pluripotent stem cells. Mechanistically, nuclear Pdha1 increases the acetyl-CoA and metabolite pool in the nucleus, leading to chromatin remodeling at pluripotency genes by enhancing histone H3 acetylation. Our results reveal an important role of mitochondrial TCA cycle enzymes in the epigenetic regulation of pluripotency that constitutes a mitochondria-to-nucleus retrograde signaling mode in different states of pluripotent acquisition. |
| 英文摘要: |
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