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BRD2 impedes iPSC reprogramming by regulating lipogenesis and matrisome.
Kejin Hu1,2, Ricardo Cevallos2, Ruowen Zhang1
1Department of Pathology, University of Alabama at Birmingham, AL.
Research Square
|December 11, 2025
Summary
BRD2 suppresses lipogenesis, hindering human pluripotent stem cell (HiPSC) reprogramming. Enhancing lipogenesis or supplementing lipids promotes HiPSC generation, revealing BRD2
Area of Science:
- Stem Cell Biology
- Epigenetics
- Metabolic Regulation
Background:
- Human pluripotent stem cell (HiPSC) induction from somatic cells faces poorly understood barriers.
- The role of lipids in cellular reprogramming remains largely unexplored.
- BRD2's function in regulating lipogenesis and the matrisome program during reprogramming is unknown.
Purpose of the Study:
- To investigate the role of BRD2 in human pluripotent stem cell (HiPSC) reprogramming.
- To elucidate the mechanisms by which BRD2 influences lipogenesis and the matrisome program.
- To determine if modulating lipogenesis can overcome reprogramming barriers.
Main Methods:
- Assessing BRD2's impact on lipogenesis and somatic transcriptional programs during reprogramming.
- Analyzing the effects of SCD and HMGCR (lipogenesis enzymes) on iPSC reprogramming.
- Investigating the influence of lipid supplementation on reprogramming efficiency.
- Examining BRD2's binding to lipogenesis genes and its regulation of H3K27Ac status.
Main Results:
- BRD2 acts as a barrier to HiPSC reprogramming by suppressing lipogenesis.
- BRD2 maintains the somatic transcriptional program, including the matrisome program.
- Upregulating lipogenesis enzymes (SCD, HMGCR) or supplementing lipids enhances iPSC reprogramming.
- BRD2's ET tail suppresses reprogramming and lipogenesis but positively regulates the matrisome program.
- BRD2 binds to lipogenesis genes and negatively regulates their H3K27Ac levels.
Conclusions:
- BRD2 suppresses lipogenesis, presenting a barrier to HiPSC reprogramming.
- Targeting lipogenesis pathways or lipid supplementation can promote HiPSC generation.
- BRD2 exhibits opposing regulatory roles on matrisome and lipogenesis, impacting reprogramming outcomes.
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