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Series GSE40594 Query DataSets for GSE40594
Status Public on Nov 13, 2014
Title Localization of the Rb tumor suppressor in MEFs during reprogramming to iPS and the consequence of Rb loss on the transcriptional profile and histone landscape in these cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The reprogramming of differentiated cells to an embryonic stem cell-like state provides a powerful system to explore fundamental mechanisms of development, including how mammalian cells establish and maintain pluripotency and long-term self-renewal capability. Based on the similarities between embryonic stem cells and cancer cells, we investigated the potential role of the retinoblastoma tumor suppressor and cell cycle regulator RB in the reprogramming of fibroblasts into induced pluripotent stem cells (iPS cells). Herein we demonstrate that loss of RB function leads to both an acceleration of the reprogramming process and the generation of more iPS clones from fibroblasts. This effect is largely due to a restrictive role for RB at the early stages of reprogramming. Surprisingly, however, RB inactivation does not enhance the formation of iPS clones by accelerating the proliferation of cells undergoing reprogramming. Rather, a genome-wide investigation of RB targets indicates that RB binds to regulatory regions of pluripotency genes such as Sox2 and Oct4 and contributes to their full repression in differentiated cells. This effect correlates with the maintenance of a repressive chromatin structure at these loci. Accordingly, Rb-deficient fibroblasts can be reprogrammed into iPS cells even in the absence of exogenous Sox2, which is normally required to initiate reprogramming from fibroblasts. These experiments identify a novel barrier in the reprogramming process, mainly the repression of certain pluripotency genes such as Sox2 by RB, which provides a new link between tumor suppressor mechanisms and cellular reprogramming.
Overall design RNAseq from MEFs with 2 biological replicates (save CP), Rb ChIPseq from MEFs with 2 biological replicates, Histone H3 modification ChIPseq from MEFs with 1 biological replicate
Contributor(s) Kareta MS, Gorges LL, Hafeez S, Spacek D, Batista LF, Vaka D, Artandi SE, Sage J, Wernig M
Citation(s) 25467916
Submission date Sep 04, 2012
Last update date May 15, 2019
Contact name Julien Sage
Phone (650) 723-5113
Organization name Stanford University
Department Pediatrics
Lab Sage
Street address 265 Campus Drive, SIM1 G2078
City Stanford
State/province CA
ZIP/Postal code 94305-5457
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (18)
GSM997573 GFP-infected cKO MEFs RNAseq
GSM997574 GFP-infected with 4F cKO MEFs RNAseq
GSM997575 Cre-infected cKO MEFs RNAseq biological replicate 2
BioProject PRJNA174435
SRA SRP015417

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Supplementary file Size Download File type/resource
GSE40594_RAW.tar 74.0 Mb (http)(custom) TAR (of BED, WIG)
GSE40594_genes.fpkm_tracking.gz 2.4 Mb (ftp)(http) FPKM_TRACKING
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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