miRNA-mediated control of exogenous OCT4 during mesenchymal-epithelial transition increases measles vector reprogramming efficiency

Ramya Rallabandi, Brenna Sharp, Conrad Cruz, Qi Wang, Alexis Locsin, Christopher B. Driscoll, Ella Lee, Tim Nelson, Patricia Devaux

Research output: Contribution to journalArticlepeer-review

Abstract

OCT4 is a key mediator of induced pluripotent stem cell (iPSC) reprogramming, but the mechanistic insights into the role of exogenous OCT4 and timelines that initiate pluripotency remain to be resolved. Here, using measles reprogramming vectors, we present microRNA (miRNA) targeting of exogenous OCT4 to shut down its expression during the mesenchymal to the epithelial transition phase of reprogramming. We showed that exogenous OCT4 is required only for the initiation of reprogramming and is dispensable for the maturation stage. However, the continuous expression of SOX2, KLF4, and c-MYC is necessary for the maturation stage of the iPSC. Additionally, we demonstrate a novel application of miRNA targeting in a viral vector to contextually control the vector/transgene, ultimately leading to an improved reprogramming efficiency. This novel approach could be applied to other systems for improving the efficiency of vector-induced processes.

Original languageEnglish (US)
Pages (from-to)48-61
Number of pages14
JournalMolecular Therapy - Methods and Clinical Development
Volume24
DOIs
StatePublished - Mar 10 2022

Keywords

  • OCT4
  • iPSC
  • measles virus
  • mesenchymal-epithelial transition
  • microRNA targeting
  • reprogramming
  • viral vectors

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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