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Series GSE52373 Query DataSets for GSE52373
Status Public on Nov 17, 2013
Title C/EBPα poises B cells for rapid reprogramming into iPS cells [ChIP-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary C/EBPα induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem cells (iPSCs) when co-expressed with Oct4, Sox2, Klf4 and Myc (OSKM). However, how C/EBPα accomplishes these effects is unclear. We now found that transient C/EBPα expression followed by OSKM activation induces a 100 fold increase in iPSC reprogramming efficiency, involving 95% of the cells. During this conversion pluripotency and epithelial-mesenchymal transition genes become dramatically up-regulated and 60% of the cells express Oct4 within 2 days. C/EBPα acts as a pathbreaker since it transiently makes the chromatin of pluripotency genes more accessible to DNase I. It also induces the expression of the dioxygenase Tet2 and promotes its translocation to the nucleus where it binds to regulatory regions of pluripotency genes that become demethylated following OSKM induction. In line with these findings, overexpression of Tet2 enhances OSKM‐induced B cell reprogramming. Since the enzyme is also required for efficient C/EBPα-induced immune cell conversion, our data suggest that Tet2 provides a mechanistic link between iPSC reprogramming and B cell transdifferentiation. The rapid iPS reprogramming approach described should help to fully elucidate the process and has potential clinical applications.
 
Overall design Change in Cebpa genome binding/occupancy, comparing primary B-cells treated with estradiol for 18h to induce C/EBPa to untreated cells.
 
Contributor(s) Di Stefano B, Graf T
Citation(s) 24336202
Submission date Nov 14, 2013
Last update date May 15, 2019
Contact name Bruno Di Stefano
E-mail(s) distefanob@gmail.com
Organization name Harvard University
Department Harvard Dept. of Stem Cell and Regenerative Biology
Street address 185 Cambridge Street
City Boston
State/province Ma
ZIP/Postal code 02114
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM1264229 Bcells_untreated_ChIPseq_Cebpa
GSM1264230 Bcells_18hEstradiol_ChIPseq_Cebpa
This SubSeries is part of SuperSeries:
GSE52397 C/EBPα poises B cells for rapid reprogramming into iPS cells
Relations
BioProject PRJNA227547
SRA SRP032992

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Supplementary file Size Download File type/resource
GSE52373_RAW.tar 30.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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