Journal
CELL STEM CELL
Volume 22, Issue 2, Pages 252-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2017.12.001
Keywords
-
Categories
Funding
- Gladstone Institutes, National Natural Science Foundation of China [91519318]
- National Key R&D Program of China [2017YFA0104000]
- Pew Scholar Foundation
- Alfred P. Sloan Foundation
- NIH Director's Early Independent Award [OD017887]
Ask authors/readers for more resources
Generation of induced pluripotent stem cells typically requires the ectopic expression of transcription factors to reactivate the pluripotency network. However, it remains largely unclear what remodeling events on endogenous chromatin trigger reprogramming toward induced pluripotent stem cells (iPSCs). Toward this end, we employed CRISPR activation to precisely target and remodel endogenous gene loci of Oct4 and Sox2. Interestingly, we found that single-locus targeting of Sox2 was sufficient to remodel and activate Sox2, which was followed by the induction of other pluripotent genes and establishment of the pluripotency network. Simultaneous remodeling of the Oct4 promoter and enhancer also triggered reprogramming. Authentic pluripotent cell lines were established in both cases. Finally, we showed that targeted manipulation of histone acetylation at the Oct4 gene locus could also initiate reprogramming. Our study generated authentic iPSCs with CRISPR activation through precise epigenetic remodeling of endogenous loci and shed light on how targeted chromatin remodeling triggers pluripotency induction.
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