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| Status |
Public on Jan 15, 2009 |
| Title |
Gene expression in b1-integrin wild-type and knockout mouse heart |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
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| Overall design |
To investigate the mechanisms responsible for the abnormalities in b1 integrin mutant mice, we performed mRNA expression microarray analyses of E12.5 wild-type and mutant hearts, well before any obvious dysfunction. RNA was isolated from wild-type and mutant hearts, and arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of WT and KO mouse hearts.
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| Contributor(s) |
Ieda M, Yeh R, Srivastava D |
| Citation(s) |
19217425 |
| Submission date |
Jan 13, 2009 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Masaki Ieda |
| E-mail(s) |
mieda@gladstone.ucsf.edu
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| Phone |
415-734-2880
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| Organization name |
Gladstone Institute
|
| Street address |
1650 Owens street,
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94404 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA114503 |
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