Attenuating IPSC Reprogramming Stress with Dominant-negative BET Peptides

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jan 24

PMID 36691621

Authors

Md Emon Hossain

Ricardo Raul Cevallos

Ruowen Zhang

Kejin Hu

Affiliations

Soon will be listed here.

Abstract

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.

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