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Peer-reviewedCC BY-NC-NDCommunications biology

BRD2 impedes iPSC reprogramming by regulating lipid biosynthesis and the matrisome via its ET tail.

  • Ricardo Raul Cevallos1,2
  • Ruowen Zhang2,3
  • Rajpal Sian4
  • Shu G Chen1
  • Kejin Hu5,6
6 affiliations
  1. 1Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
  2. 2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
  3. 3Medicilon US Corp, Lexington, MA, USA.
  4. 4Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.
  5. 5Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. [email protected].
  6. 6Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA. [email protected].
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Abstract

Induction of human pluripotent stem cells (hiPSCs) from somatic cells encounters significant barriers that remain poorly understood. Lipids are fundamental cellular molecules with many essential roles. However, the roles of lipids in reprogramming are unknown. Here, we show that BRD2 is a barrier to hiPSC reprogramming by suppressing lipid genes and maintaining the somatic transcriptional program, particularly the somatic matrisome program. Strikingly, the acetylation epigenetic reader BRD2 unorthodoxly suppresses the expression of lipid-related genes in the reprogramming cells. The two rate-limiting enzymes of lipid biosynthesis, stearoyl-CoA desaturase (SCD), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), and lipid supplements all enhance iPSC reprogramming. Interestingly, the extra terminal (ET) tail of BRD2 suppresses reprogramming and the lipid transcriptional program but positively regulates the matrisome program. In line with its transcriptional suppression of lipid genes, BRD2 binds to genes of lipid biosynthesis and negatively regulates their H3K27Ac status. These discoveries advance our molecular understanding of hiPSC reprogramming, as well as of the transcriptional regulation of matrisome and lipid programs.

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Cite

BibTeXRIS
BibTeX
@article{cevallos2026brd2,
  title = {{BRD2 impedes iPSC reprogramming by regulating lipid biosynthesis and the matrisome via its ET tail.}},
  author = {Ricardo Raul Cevallos and Ruowen Zhang and Rajpal Sian and Shu G Chen and Kejin Hu},
  journal = {Communications biology},
  year = {2026},
  month = aug,
  doi = {10.1038/s42003-026-10691-1},
  url = {https://europepmc.org/article/MED/42834078},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - BRD2 impedes iPSC reprogramming by regulating lipid biosynthesis and the matrisome via its ET tail.
AU  - Ricardo Raul Cevallos
AU  - Ruowen Zhang
AU  - Rajpal Sian
AU  - Shu G Chen
AU  - Kejin Hu
PY  - 2026
DA  - 2026/08/24
JO  - Communications biology
DO  - 10.1038/s42003-026-10691-1
UR  - https://europepmc.org/article/MED/42834078
AB  - Induction of human pluripotent stem cells (hiPSCs) from somatic cells encounters significant barriers that remain poorly understood. Lipids are fundamental cellular molecules with many essential roles. However, the roles of lipids in reprogramming are unknown. Here, we show that BRD2 is a barrier to hiPSC reprogramming by suppressing lipid genes and maintaining the somatic transcriptional program, particularly the somatic matrisome program. Strikingly, the acetylation epigenetic reader BRD2 unorthodoxly suppresses the expression of lipid-related genes in the reprogramming cells. The two rate-limiting enzymes of lipid biosynthesis, stearoyl-CoA desaturase (SCD), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), and lipid supplements all enhance iPSC reprogramming. Interestingly, the extra terminal (ET) tail of BRD2 suppresses reprogramming and the lipid transcriptional program but positively regulates the matrisome program. In line with its transcriptional suppression of lipid genes, BRD2 binds to genes of lipid biosynthesis and negatively regulates their H3K27Ac status. These discoveries advance our molecular understanding of hiPSC reprogramming, as well as of the transcriptional regulation of matrisome and lipid programs.
SN  - 2399-3642
ER  -