Journal
STEM CELL REPORTS
Volume 6, Issue 5, Pages 704-716Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2016.02.004
Keywords
-
Categories
Funding
- Boehringer Ingelheim Fonds predoctoral fellowship
- MGH Tosteson fellowship
- NIH [1F32HD078029-01A1, GM44664, AG011085, HD058013]
- PRCRP at the Department of Defense [CA 120212]
- Intramural Research Program at the National Institute of Environmental Health Sciences [Z01ES102745]
- Gerald and Darlene Jordan Endowment
- Early Career Award from Howard Hughes Medical Institute
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available