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| Status |
Public on Dec 10, 2015 |
| Title |
CAF-1 safeguards somatic cell identity during factor-induced reprogramming |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Cellular differentiation involves profound changes in the chromatic landscape, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNAi screens targeting chromatin factors during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Suppression of CAF-1 increased reprogramming efficiency by several orders of magnitude and facilitated iPSC formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as a novel regulator of somatic cell identity during transcription factor-induced cell fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.
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| |
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| Overall design |
Gene expression analysis in CAF-1 knockdown and Renilla control during early OKSM-induced reprogramming by microarray
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| |
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| Contributor(s) |
Hochedlinger K, Cheloufi S |
| Citation(s) |
26659182 |
| Submission date |
Sep 04, 2015 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Peter J Park |
| E-mail(s) |
peter_park@harvard.edu
|
| Phone |
617-432-7373
|
| Organization name |
Harvard Medical School
|
| Department |
Center for Biomedical Informatics
|
| Street address |
10 Shattuck St
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (12)
|
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| This SubSeries is part of SuperSeries: |
| GSE66534 |
The histone chaperone CAF-1 safeguards somatic cell identity during transcription factor-induced reprogramming |
|
| Relations |
| BioProject |
PRJNA294797 |
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