Attenuating iPSC reprogramming stress with dominant-negative BET peptides

Md Emon Hossain, Ricardo Raul Cevallos, Ruowen Zhang, Kejin Hu

Research output: Contribution to journalArticlepeer-review


Generation of induced pluripotent stem cells (iPSCs) is inefficient and stochastic. The underlying causes for these deficiencies are elusive. Here, we showed that the reprogramming factors (OCT4, SOX2, and KLF4, collectively OSK) elicit dramatic reprogramming stress even without the pro-oncogene MYC including massive transcriptional turbulence, massive and random deregulation of stress-response genes, cell cycle impairment, downregulation of mitotic genes, illegitimate reprogramming, and cytotoxicity. The conserved dominant-negative (DN) peptides of the three ubiquitous human bromodomain and extraterminal (BET) proteins enhanced iPSC reprogramming and mitigated all the reprogramming stresses mentioned above. The concept of reprogramming stress developed here affords an alternative avenue to understanding and improving iPSC reprogramming. These DN BET fragments target a similar set of the genes as the BET chemical inhibitors do, indicating a distinct approach to targeting BET proteins.

Original languageEnglish
Article number105889
Issue number1
StatePublished - 20 Jan 2023


  • Peptides
  • Protein
  • Stem cell plasticity
  • Stem cells research


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