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Cpt1a Drives Primed-to-naïve Pluripotency Transition Through Lipid Remodeling

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Journal Commun Biol
Specialty Biology
Date 2024 Sep 30
PMID 39349670
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Abstract

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.

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References
1.
Brons I, Smithers L, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes S . Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 2007; 448(7150):191-5. DOI: 10.1038/nature05950. View

2.
Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

3.
Zhou W, Jiang D, Tian J, Liu L, Lu T, Huang X . Acetylation of H3K4, H3K9, and H3K27 mediated by p300 regulates the expression of GATA4 in cardiocytes. Genes Dis. 2020; 6(3):318-325. PMC: 6997570. DOI: 10.1016/j.gendis.2018.10.002. View

4.
Lasko L, Jakob C, Edalji R, Qiu W, Montgomery D, DiGiammarino E . Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017; 550(7674):128-132. PMC: 6050590. DOI: 10.1038/nature24028. View

5.
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N . Acetate controls endothelial-to-mesenchymal transition. Cell Metab. 2023; 35(7):1163-1178.e10. PMC: 10529701. DOI: 10.1016/j.cmet.2023.05.010. View