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Status |
Public on Nov 17, 2013 |
Title |
C/EBPα poises B cells for rapid reprogramming into iPS cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing
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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.
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Overall design |
Refer to individual Series
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Citation(s) |
24336202, 25977766 |
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Submission date |
Nov 14, 2013 |
Last update date |
Jul 31, 2019 |
Contact name |
Bruno Di Stefano |
E-mail(s) |
distefanob@gmail.com
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Organization name |
Baylor College of Medicine
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Department |
Molecular and Cellular Biology
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Street address |
1 Baylor Plaza
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City |
Houston |
State/province |
TX |
ZIP/Postal code |
77030 |
Country |
USA |
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Platforms (2) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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Samples (48)
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GSM1128619 |
18hrs pulse B cells, time 0, technical replicate 1 |
GSM1128620 |
18hrs pulse B cells, time 0, technical replicate 2 |
GSM1128621 |
18hrs pulse B cells, time 48, technical replicate 1 |
GSM1128622 |
18hrs pulse B cells,time 48, technical replicate 2 |
GSM1128623 |
18hrs pulse B cells,time 96, technical replicate 1 |
GSM1128624 |
18hrs pulse B cells, time 96, technical replicate 2 |
GSM1128625 |
18hrs pulse B cells,time 144, technical replicate 1 |
GSM1128626 |
18hrs pulse B cells, time 144, technical replicate 2 |
GSM1128627 |
18hrs pulse B cells,time 192, technical replicate 1 |
GSM1128628 |
18hrs pulse B cells, time 192, technical replicate 2 |
GSM1128629 |
B cells, time 0, technical replicate 1 |
GSM1128630 |
B cells, time 0, technical replicate 2 |
GSM1128631 |
B cells, time 48, technical replicate 1 |
GSM1128632 |
B cells, time 48, technical replicate 2 |
GSM1128633 |
B cells, time 96, technical replicate 1 |
GSM1128634 |
B cells,time 96, technical replicate 2 |
GSM1128635 |
B cells, time 144, technical replicate 1 |
GSM1128636 |
B cells, time 144, technical replicate 2 |
GSM1128637 |
B cells, time 192, technical replicate 1 |
GSM1128638 |
B cells, time 192, technical replicate 2 |
GSM1128639 |
ES cells R1, technical replicate 1 |
GSM1128640 |
aiPS cells #8, technical replicate 1 |
GSM1128641 |
ES cells Bruce, technical replicate 1 |
GSM1128642 |
ES cells Bruce, technical replicate 2 |
GSM1128643 |
iPS cells #26, technical replicate 1 |
GSM1128644 |
iPS cells #26, technical replicate 2 |
GSM1128645 |
aiPS cells #22, technical replicate 1 |
GSM1128646 |
aiPS cells #22, technical replicate 2 |
GSM1264229 |
Bcells_untreated_ChIPseq_Cebpa |
GSM1264230 |
Bcells_18hEstradiol_ChIPseq_Cebpa |
GSM1264669 |
Bcells_untreated_RNAseq |
GSM1264670 |
Bcells_18hEstradiol_RNAseq |
GSM1359910 |
18hrs pulse B cells, time 3, technical replicate 1 |
GSM1359911 |
18hrs pulse B cells, time 3, technical replicate 2 |
GSM1359912 |
18hrs pulse B cells, time 6, technical replicate 1 |
GSM1359913 |
18hrs pulse B cells, time 6, technical replicate 2 |
GSM1359914 |
18hrs pulse B cells, time 12, technical replicate 1 |
GSM1359915 |
18hrs pulse B cells, time 12, technical replicate 2 |
GSM1359916 |
18hrs pulse B cells, time 24, technical replicate 1 |
GSM1359917 |
18hrs pulse B cells, time 24, technical replicate 2 |
GSM1359918 |
B cells, time 3, technical replicate 1 |
GSM1359919 |
B cells, time 3, technical replicate 2 |
GSM1359920 |
B cells, time 6, technical replicate 1 |
GSM1359921 |
B cells, time 6, technical replicate 2 |
GSM1359922 |
B cells, time 12, technical replicate 1 |
GSM1359923 |
B cells, time 12, technical replicate 2 |
GSM1359924 |
B cells, time 24, technical replicate 1 |
GSM1359925 |
B cells, time 24, technical replicate 2 |
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This SuperSeries is composed of the following SubSeries: |
GSE46321 |
C/EBPα poises B cells for rapid reprogramming into iPS cells [array] |
GSE52373 |
C/EBPα poises B cells for rapid reprogramming into iPS cells [ChIP-Seq] |
GSE52396 |
C/EBPα poises B cells for rapid reprogramming into iPS cells [RNA-Seq] |
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Relations |
BioProject |
PRJNA227776 |
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