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Cellular and Molecular Life Sciences

Cellular and Molecular Life Sciences

IF: 6.2
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BRG1 improves reprogramming efficiency by enhancing glycolytic metabolism

Published:6 December 2024 DOI: 10.1007/s00018-024-05527-2 PMID: 39643758
Xuan Ren,?Shihai Huang,?Jianchun Xu,?Qingsong Xue,?Tairan Xu,?Deshun Shi,?Shinan Ma,?Xiangping Li

Abstract

BRG1 has been found to promote the generation of induced pluripotent stem cells (iPSCs) by regulating epigenetic modifications or binding to transcription factors, however, the role of BRG1 on the cellular metabolism during reprogramming has not been reported. In this study, we found that BRG1 improved the efficiency of porcine iPSC generation, and upregulated the expression of pluripotency-related factors. Further analysis revealed that BRG1 promoted cellular glycolysis, and increased levels of glycolysis-related metabolites. It enhanced the transcriptional activity of glycolysis-related gene HK2, PKM2, and PFK-1 promoters, and decreased the enrichment of H3K9me3 in glycolysis- and pluripotency-related gene promoters. BRG1 also increased the phosphorylation level at the Ser473 site of AKT protein. The specific PI3K/AKT signaling pathway inhibitor, LY294002, impaired the generation of porcine iPSCs, downregulated the expression of pluripotency-related factors, and inhibited cellular glycolysis, overexpressing BRG1 rescued those changes caused by LY294002 treatment. In addition, the glycolysis inhibitor 2-DG and BRG1 inhibitor PFI-3 had similar effects to LY294002. The above results suggest that overexpression of BRG1 promotes the generation of porcine iPSCs by facilitating glycolytic reprogramming through the PI3K/AKT signaling pathway.

Substances (2)

Materials
Procduct Name CAS Molecular Formula Supplier Price
LY 294002 HYDROCHLORIDE 154447-36-6 C19H17NO3 299 suppliers $20.00-$3350.00
HEXADIMETHRINE BROMIDE 28728-55-4 C39H90Br6N6X2 64 suppliers $65.10-$950.00

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