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Status |
Public on Nov 17, 2013 |
Title |
C/EBPα poises B cells for rapid reprogramming into iPS cells [array] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Somatic cell reprogramming into pluripotent stem cells induced by Oct4, Sox2, Klf4 and Myc (OSKM) occurs at low frequencies and with a considerable delay involving a stochastic phase. In contrast, transdifferentiation of B cells into macrophages induced by C/EBPα is fully efficient and initiated almost immediately. We now discovered that a pulse of C/EBPα in B cell precursors followed by OSKM expression dramatically enhances reprogramming to pluripotency, overcoming the stochastic phase. The cells simultaneously activate mesenchymal-epithelial transition and pluripotency genes to high levels within 2 days, correlating with promoter demethylation and accessibility to Oct4 binding. The conditioning effect of C/EBPα is shared with C/EBPβ but not with transcription factors that induce erythroid, neuronal and muscle fates, which are innocuous or inhibitory. Surprisingly, OSKM induce the transient upregulation of macrophage genes in B cells, including Cebpa and Cebpb, as well as trophectoderm genes. Since both C/EBPs are functionally expressed in trophoblasts their unique pluripotency-conditioning capacity might reflect an early embryonic function. Our findings have removed a major hurdle in elucidating mechanisms that establish pluripotency.
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Overall design |
Change in gene expression during reprogramming of B-cells into iPS cells, comparing the time 0h (B-cells) to cells induced with OKSM, pre-treated or not with estradiol to induce C/EBPa, at different time points.
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Contributor(s) |
Di Stefano B, Graf T |
Citation(s) |
24336202, 25977766 |
Submission date |
Apr 23, 2013 |
Last update date |
Jul 31, 2019 |
Contact name |
Bruno Di Stefano |
E-mail(s) |
distefanob@gmail.com
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Organization name |
Harvard University
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Department |
Harvard Dept. of Stem Cell and Regenerative Biology
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Street address |
185 Cambridge Street
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City |
Boston |
State/province |
Ma |
ZIP/Postal code |
02114 |
Country |
USA |
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Platforms (1) |
GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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Samples (44)
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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 |
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 SubSeries is part of SuperSeries: |
GSE52397 |
C/EBPα poises B cells for rapid reprogramming into iPS cells |
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Relations |
BioProject |
PRJNA198734 |
Supplementary file |
Size |
Download |
File type/resource |
GSE46321_RAW.tar |
528.6 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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