A microRNA network regulates proliferative timing and extracellular matrix synthesis during cellular quiescence in fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42614 | GEO | 2012/12/05
SECONDARY ACCESSION(S): PRJNA182356
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC3924601 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-12-05 | E-GEOD-42614 | biostudies-arrayexpress
Project description: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. microRNAs in human neonatal dermal fibroblasts in 3 cell cycle conditions (proliferating, 4 days serum starved, 7 days contact inhibited) were analyzed by one color microarray. 3 separate fibroblast cell lines from different human donors were analyzed for each condition, with two separate labeling and hybridization samples for each cell line. In total, 18 samples were hybridized to the microRNA microarray.
2012-12-05 | E-GEOD-42593 | biostudies-arrayexpress
Project description: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. 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.
2012-12-05 | E-GEOD-42613 | biostudies-arrayexpress
Project description: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.
2012-12-05 | GSE42613 | GEO
Project description: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.
2012-12-05 | GSE42593 | GEO
Project description: Not available
| S-EPMC6466771 | biostudies-literature
Project description: Not available
| S-EPMC2583333 | biostudies-literature
Project description:Fibroblasts are the main producers of extracellular matrix (ECM) responsible for ECM maintenance and repair, a process often disrupted in chronic lung diseases. The accompanying mechanical changes adversely affect resident cells and overall lung function. Numerous models have been used to elucidate fibroblast behavior which are now evolving towards complex 3D models incorporating ECM, aiming to replicate the cells’ native environment. Little is known about the cellular changes that occur when moving from 2D to 3D cell culture. This study compared gene expression profiles of primary human lung fibroblasts from 7 subjects with normal lung function, cultured for 24 hours on 2D collagen I-coated tissue culture plastic and in 3D collagen I hydrogels, which are commonly used to mimic ECM in various models, from contraction assays to organ-on-a-chip models. Comparing 3D to 2D cell culture, 6,771 differentially expressed genes (2,896 up, 3,875 down) were found; enriched gene sets within the downregulated genes, identified through Gene Set Enrichment Analysis and Ingenuity pathway analysis, were involved in the initiation of DNA replication which implied downregulation of fibroblast proliferation in 3D. Observation of cells for 72 hours in 2D and 3D environments confirmed the reduced progression through the cell cycle in 3D. A focused analysis examining the Hippo pathway and ECM-associated genes, showed differential patterns of gene expression in the 3D versus 2D culture. Altogether, the transcriptional response of fibroblasts cultured in 3D indicated inhibition of proliferation, and alterations in Hippo and ECM pathways indicating a complete switch from proliferation to ECM remodeling.
2023-11-13 | GSE247220 | GEO
Project description: Not available
| S-EPMC9236907 | biostudies-literature