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Status |
Public on Dec 05, 2012 |
Title |
A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts [mRNA] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Background: Although quiescence—reversible cell-cycle arrest—is a key part in the life history and fate of many mammalian cell types, the mechanisms of gene regulation in quiescent cells are poorly understood. We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts. Results: Using microarrays, we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts. Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles, indicating common changes induced by distinct quiescence signals. By analyzing the gene expression patterns of microRNA target genes with quiescence, we discovered a strong regulatory function for miR-29, which is downregulated with quiescence. Using microarrays and immunoblotting, we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence. In addition, overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence. We also found that let-7 and miR-125 were upregulated in quiescent cells. Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence, while the combination of both together slowed cell cycle re-entry even further. Conclusions: microRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles, in particular, the induction of extracellular matrix proteins in quiescent fibroblasts.
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Overall design |
mRNAs were analyzed by two color microarray from three separate human neonatal dermal fibroblasts cell lines transfected either with a miR-29b mimic or a control short dsRNA. One sample was labeled and analyzed in duplicate to ensure consistency in labeling and hybridization technique.
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Contributor(s) |
Suh EJ, Remillard MY, Legesse-Miller A, Johnson E, Lemons JM, Chapman TR, Forman JJ, Kojima M, Silberman ES, Coller HA |
Citation(s) |
23259597 |
Submission date |
Nov 29, 2012 |
Last update date |
Jan 23, 2019 |
Contact name |
Eric Jungwoo Suh |
Organization name |
Princeton University
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Department |
Molecular Biology
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Lab |
Coller Lab
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Street address |
14 Washington Rd
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City |
Princeton |
State/province |
NJ |
ZIP/Postal code |
08544 |
Country |
USA |
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Platforms (1) |
GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE42614 |
A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts |
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Relations |
BioProject |
PRJNA182357 |