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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 19, 2015 |
| Title |
Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells that Contribute to the Fibrous Cap |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including “vascular disease,” “disorder of artery,” and “occlusion of artery” as well as disease-related cellular functions including “cellular movement,” and “cellular growth and proliferation.” In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.
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| Overall design |
RNA-Seq: 3 versus 3 technical replicates, siControl versus siTCF21
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| Contributor(s) |
Nurnberg ST, Cheng K, Raiesdana A, Kundu R, Miller CL, Kim JB, Arora K, Carcamo-Oribe I, Xiong Y, Tellakula N, Nanda V, Murthy N, Boisvert WA, Hedin U, Perisic L, Aldi S, Maegdefessel L, Pjanic M, Owens GK, Tallquist MD, Quertermous T |
| Citation(s) |
26020946, 26090325 |
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| Submission date |
Feb 21, 2013 |
| Last update date |
Jul 30, 2019 |
| Contact name |
Sylvia T Nurnberg |
| E-mail(s) |
sylvian@upenn.edu
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| Organization name |
University of Pennsylvania
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| Department |
Medicine
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| Lab |
Rader
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| Street address |
3400 Civic Center Blvd
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| GSM1085736 |
non-silencing control siRNA technical replicate 1 |
| GSM1085737 |
non-silencing control siRNA technical replicate 2 |
| GSM1085738 |
non-silencing control siRNA technical replicate 3 |
| GSM1085739 |
TCF21 knockdown siRNA technical replicate 1 |
| GSM1085740 |
TCF21 knockdown siRNA technical replicate 2 |
| GSM1085741 |
TCF21 knockdown siRNA technical replicate 3 |
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| Relations |
| SRA |
SRP018779 |
| BioProject |
PRJNA191801 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44461_RAW.tar |
3.3 Gb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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