Cpt1a Drives primed-to-naïve pluripotency transition through lipid remodeling
Metabolism has been implicated in cell fate determination, particularly through epigenetic modifications. Similarly, lipid remodeling also plays a role in regulating cell fate. Here, we present comprehensive lipidomics analysis during BMP4-driven primed to naive pluripotency transition or BiPNT and demonstrate that lipid remodeling plays an essential role. We further identify Cpt1a as a rate-limiting factor in BiPNT, driving lipid remodeling and metabolic reprogramming while simultaneously increasing intracellular acetyl-CoA levels and enhancing H3K27ac at chromatin open sites. Perturbation of BiPNT by histone acetylation inhibitors suppresses lipid remodeling and pluripotency transition. Together, our study suggests that lipid remodeling promotes pluripotency transitions and further regulates cell fate decisions, implicating Cpt1a as a critical regulator between primed-naive cell fate control.
Authors
- Duanqing Pei (ORCID: https://orcid.org/0000-0002-5222-014X)
- Zechuan Liang (ORCID: https://orcid.org/0009-0004-4292-6992)
- Ziwei Zhai (ORCID: https://orcid.org/0000-0002-8892-5491)
- Chengchen Zhao (ORCID: https://orcid.org/0000-0002-8454-6347)
- Xingnan Huang (ORCID: https://orcid.org/0000-0003-0795-7596)
- Wei Li (ORCID: https://orcid.org/0000-0001-7864-404X)
- Bo Wang (ORCID: https://orcid.org/0000-0003-1182-952X)
- Tao Huang (ORCID: https://orcid.org/0000-0002-0879-1850)
- Yue Qin (ORCID: https://orcid.org/0000-0002-6824-6491)
- Zhaoyi Ma
- Qiannan Wang (ORCID: https://orcid.org/0000-0002-7972-0718)
- Pengli Li (ORCID: https://orcid.org/0000-0002-5878-7681)
- Ming Jin (ORCID: https://orcid.org/0000-0002-6666-0787)
- Junqi Kuang (ORCID: https://orcid.org/0000-0003-2681-7580)
- Xiaomin Wang (ORCID: https://orcid.org/0009-0002-6782-6571)
- Yu Fu
- Yixin Fan (ORCID: https://orcid.org/0000-0002-0529-3768)
Institutions
- Zhejiang University of Science and Technology (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Westlake University (CN)
- Zhejiang Lab (CN)
- University of Chinese Academy of Sciences (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1038/s42003-024-06874-3
- Citations
- 6
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Westlake University
- National Natural Science Foundation of China