A Serial shRNA Screen for Roadblocks to Reprogramming Identifies the Protein Modifier SUMO2. Academic Article uri icon

Overview

abstract

  • The generation of induced pluripotent stem cells (iPSCs) from differentiated cells following forced expression of OCT4, KLF4, SOX2, and C-MYC (OKSM) is slow and inefficient, suggesting that transcription factors have to overcome somatic barriers that resist cell fate change. Here, we performed an unbiased serial shRNA enrichment screen to identify potent repressors of somatic cell reprogramming into iPSCs. This effort uncovered the protein modifier SUMO2 as one of the strongest roadblocks to iPSC formation. Depletion of SUMO2 both enhances and accelerates reprogramming, yielding transgene-independent, chimera-competent iPSCs after as little as 38 hr of OKSM expression. We further show that the SUMO2 pathway acts independently of exogenous C-MYC expression and in parallel with small-molecule enhancers of reprogramming. Importantly, suppression of SUMO2 also promotes the generation of human iPSCs. Together, our results reveal sumoylation as a crucial post-transcriptional mechanism that resists the acquisition of pluripotency from fibroblasts using defined factors.

publication date

  • March 3, 2016

Research

keywords

  • Cell Differentiation
  • Induced Pluripotent Stem Cells
  • Proto-Oncogene Proteins c-myc
  • Small Ubiquitin-Related Modifier Proteins

Identity

PubMed Central ID

  • PMC4939549

Scopus Document Identifier

  • 84959302338

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2016.02.004

PubMed ID

  • 26947976

Additional Document Info

volume

  • 6

issue

  • 5