Plin2-mediated lipid droplet mobilization accelerates exit from pluripotency by lipidomic remodeling and histone acetylation
© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare..
Metabolic switch is critical for cell fate determination through metabolic functions, epigenetic modifications, and gene expression. However, the mechanisms underlying these alterations and their functional roles remain unclear. Here, we show that Plin2-mediated moderate lipid hydrolysis is critical for pluripotency of embryonic stem cells (ESCs). Upon exit from pluripotency, lipid droplet (LD)-associated protein Plin2 is recognized by Hsc70 and degraded via chaperone-mediated autophagy to facilitate LD mobilization. Enhancing lipid hydrolysis by Plin2 knockout promotes pluripotency exit, which is recovered by ATGL inhibition. Mechanistically, excessive lipid hydrolysis induces a dramatic lipidomic remodeling characterized by decreased cardiolipin and phosphatidylethanolamine, which triggers defects in mitochondrial cristae and fatty acid oxidation, resulting in reduced acetyl-CoA and histone acetylation. Our results reveal how LD mobilization is regulated and its critical role in ESC pluripotency, and indicate the mechanism linking LD homeostasis to mitochondrial remodeling and epigenetic regulation, which might shed light on development and diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Cell death and differentiation - 29(2022), 11 vom: 25. Nov., Seite 2316-2331 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yi [VerfasserIn] |
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| Links: |
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| Themen: |
Histones |
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| Anmerkungen: |
Date Completed 31.10.2022 Date Revised 02.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41418-022-01018-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341365262 |
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| 245 | 1 | 0 | |a Plin2-mediated lipid droplet mobilization accelerates exit from pluripotency by lipidomic remodeling and histone acetylation |
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| 520 | |a © 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare. | ||
| 520 | |a Metabolic switch is critical for cell fate determination through metabolic functions, epigenetic modifications, and gene expression. However, the mechanisms underlying these alterations and their functional roles remain unclear. Here, we show that Plin2-mediated moderate lipid hydrolysis is critical for pluripotency of embryonic stem cells (ESCs). Upon exit from pluripotency, lipid droplet (LD)-associated protein Plin2 is recognized by Hsc70 and degraded via chaperone-mediated autophagy to facilitate LD mobilization. Enhancing lipid hydrolysis by Plin2 knockout promotes pluripotency exit, which is recovered by ATGL inhibition. Mechanistically, excessive lipid hydrolysis induces a dramatic lipidomic remodeling characterized by decreased cardiolipin and phosphatidylethanolamine, which triggers defects in mitochondrial cristae and fatty acid oxidation, resulting in reduced acetyl-CoA and histone acetylation. Our results reveal how LD mobilization is regulated and its critical role in ESC pluripotency, and indicate the mechanism linking LD homeostasis to mitochondrial remodeling and epigenetic regulation, which might shed light on development and diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Perilipin-2 |2 NLM | |
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| 700 | 1 | |a Chen, Keshi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Linpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Zhihong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Guangsuo |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zichao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Heying |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jianghuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jinye |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Danyun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junwei |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Jinfu |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Guangjin |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Wai-Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xingguo |e verfasserin |4 aut | |
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