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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 15, 2016 |
| Title |
Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. doi: 10.1038/nm.4109 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The multiple claims about reactivation of the embryonic stem cell (ESC) pluripotency factor OCT4 in somatic cells are highly controversial due to the fact that there is no direct evidence that OCT4 has a functional role in cells other than ESCs. Herein we demonstrate that smooth muscle cell (SMC)-specific knockout of Oct4 within atherosclerotic mice resulted in increased lesion size and multiple changes consistent with decreased plaque stability. SMC-lineage tracing studies showed that lesions from SMC-specific conditional Oct4 KO mice had a reduced number of SMCs likely due to impaired SMC migration. RNA-seq analysis of lesion specimens showed that loss of Oct4 in SMCs was associated with marked activation of genes associated with inflammation and suppression of genes associated with cell migration, a number of which were shown to be activated in cultured SMCs by the combination of hypoxia and oxidized phospholipids in an OCT4-dependent manner. Activation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was HIF1α- and KLF4-dependent. Results provide the first genetic evidence that OCT4 plays a functional role in somatic cells and highlight the importance of further investigation of possible OCT4 functions in somatic cells.
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| Overall design |
In vivo: mRNA profiles of 18 week fed Western diet wild type (WT) and Oct4-/- mice were generated by deep sequencing, four animals per group, using Illumina HiSeq 2000. In vitro: a smooth muscle cell wild type (WT) and Oct4-/- (KO) primary aortic cell line was generated and used. mRNA profiles were generated by deep sequencing, in triplicates, using Illumina HiSeq 2000, for the following groups: WT-normoxia-vehicle; WT-normoxia-POVPC; KO-normoxia-vehicle; KO-normoxia-POVP; WT-hypoxia-vehicle; WT-hypoxia-POVPC; KO-hypoxia-vehicle; and KO-hypoxia-POVPC.
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| Contributor(s) |
Cherepanova OA, Gomez D, Shankman LS, Swiatlowska P, Williams J, Sarmento OF, Alencar GF, Bevard MH, Greene ES, Murgai M, Turner SD, Geng Y, Bekiranov S, Connely JJ, Tomilin A, Owens GK |
| Citation(s) |
27183216, 30814500 |
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| Submission date |
Nov 16, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Gary K Owens |
| Organization name |
University of Virginia
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| Street address |
415 Lane Road MR5 Building Room 1322
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (32)
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| GSM1941378 |
in vivo, KO 4 |
| GSM1941379 |
in vivo, WT 1 |
| GSM1941380 |
in vivo, WT 2 |
| GSM1941381 |
in vivo, WT 3 |
| GSM1941382 |
in vivo, WT 4 |
| GSM1941383 |
in vitro, WT Vehicle Normoxia 1 |
| GSM1941384 |
in vitro, WT Vehicle Normoxia 2 |
| GSM1941385 |
in vitro, WT Vehicle Normoxia 3 |
| GSM1941386 |
in vitro, WT POVPC Normoxia 1 |
| GSM1941387 |
in vitro, WT POVPC Normoxia 2 |
| GSM1941388 |
in vitro, WT POVPC Normoxia 3 |
| GSM1941389 |
in vitro, KO Vehicle Normoxia 1 |
| GSM1941390 |
in vitro, KO Vehicle Normoxia 2 |
| GSM1941391 |
in vitro, KO Vehicle Normoxia 3 |
| GSM1941392 |
in vitro, KO POVPC Normoxia 1 |
| GSM1941393 |
in vitro, KO POVPC Normoxia 2 |
| GSM1941394 |
in vitro, KO POVPC Normoxia 3 |
| GSM1941395 |
in vitro, WT Vehicle Hypoxia 1 |
| GSM1941396 |
in vitro, WT Vehicle Hypoxia 2 |
| GSM1941397 |
in vitro, WT Vehicle Hypoxia 3 |
| GSM1941398 |
in vitro, WT POVPC Hypoxia 1 |
| GSM1941399 |
in vitro, WT POVPC Hypoxia 2 |
| GSM1941400 |
in vitro, WT POVPC Hypoxia 3 |
| GSM1941401 |
in vitro, KO Vehicle Hypoxia 1 |
| GSM1941402 |
in vitro, KO Vehicle Hypoxia 2 |
| GSM1941403 |
in vitro, KO Vehicle Hypoxia 3 |
| GSM1941404 |
in vitro, KO POVPC Hypoxia 1 |
| GSM1941405 |
in vitro, KO POVPC Hypoxia 2 |
| GSM1941406 |
in vitro, KO POVPC Hypoxia 3 |
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| Relations |
| BioProject |
PRJNA302280 |
| SRA |
SRP066244 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75044_oct4-atherosclerosis-in-vivo-rnaseq-rawcounts.summary.txt.gz |
397 b |
(ftp)(http) |
TXT |
| GSE75044_oct4-atherosclerosis-in-vivo-rnaseq-rawcounts.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
| GSE75044_oct4-in-vitro-rnaseq-counts.summary.txt.gz |
719 b |
(ftp)(http) |
TXT |
| GSE75044_oct4-in-vitro-rnaseq-rawcounts.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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