Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions
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PROVIDER: PRJNA687728 | ENA |
REPOSITORIES: ENA
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Project description:Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions [miRNA-Seq]
| PRJNA687690 | ENA
Project description:Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions [RNA-Seq]
| PRJNA687730 | ENA
Project description:Myofibroblasts are the major cellular source of collagen, and their accumulation – via differentiation from fibroblasts and resistance to apoptosis – is a hallmark of tissue fibrosis. Clearance of myofibroblasts by de-differentiation and restoration of apoptosis sensitivity has the potential to reverse fibrosis. Prostaglandin E2 (PGE2) and mitogens such as fibroblast growth factor-2 (FGF2) have each been shown to de-differentiate myofibroblasts, but the resultant cellular phenotypes have neither been comprehensively characterized nor compared. Here we show that PGE2 elicited de-differentiation of human lung myofibroblasts via cAMP/PKA while FGF2 utilized MEK/ERK. The two mediators yielded transitional cells with distinct transcriptomes, with FGF2 promoting but PGE2 inhibiting proliferation and survival. The gene expression pattern in fibroblasts isolated from the lungs of mice undergoing resolution of experimental fibrosis resembled that of myofibroblasts treated with PGE2 in vitro. We conclude that myofibroblast de-differentiation can proceed via distinct programs exemplified by treatment with PGE2 and FGF2, with that occurring in vivo most closely resembling the former.
2021-03-23 | GSE163831 | GEO
Project description:Myofibroblasts are the major cellular source of collagen, and their accumulation – via differentiation from fibroblasts and resistance to apoptosis – is a hallmark of tissue fibrosis. Clearance of myofibroblasts by de-differentiation and restoration of apoptosis sensitivity has the potential to reverse fibrosis. Prostaglandin E2 (PGE2) and mitogens such as fibroblast growth factor-2 (FGF2) have each been shown to de-differentiate myofibroblasts, but the resultant cellular phenotypes have neither been comprehensively characterized nor compared. Here we show that PGE2 elicited de-differentiation of human lung myofibroblasts via cAMP/PKA while FGF2 utilized MEK/ERK. The two mediators yielded transitional cells with distinct transcriptomes, with FGF2 promoting but PGE2 inhibiting proliferation and survival. The gene expression pattern in fibroblasts isolated from the lungs of mice undergoing resolution of experimental fibrosis resembled that of myofibroblasts treated with PGE2 in vitro. We conclude that myofibroblast de-differentiation can proceed via distinct programs exemplified by treatment with PGE2 and FGF2, with that occurring in vivo most closely resembling the former.
2021-03-23 | GSE163824 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-23 | GSE163832 | GEO
Project description: Not available
| S-EPMC8026183 | biostudies-literature
Project description:De- and re-differentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and re-differentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion, and the expression of key developmental markers, challenges the physiological relevance of this culture system.
2016-06-01 | E-MTAB-4800 | biostudies-arrayexpress
Project description:Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumour progression. Myofibroblasts have previously mostly been distinguished from normal fibroblasts only by the expression of α smooth muscle actin (αSMA). We now identify AOC3, a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast reacting monoclonal antibody (mAb), PR2D3. The normal and tumour tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by non-enzymatic procedures. Whole genome microarray mRNA expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly expressed differentially between these two cell types; NKX2-3 and LRRC17 are expressed in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. Transforming Growth Factor β (TGFβ) substantially down-regulated AOC3 expression in myofibroblasts but not in skin fibroblasts, in which it dramatically increased the expression of αSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and an increased expression of the fibroblast associated gene, SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3 and other markers, are a distinctly different cell type from TGFβ activated fibroblasts. colorectal myofibroblast specific markers and expression profiles were sought by comparing four primary myofibroblast cultures to a panel of four dermal and foreskin fibroblast cell lines Four primary myofibroblast cultures established from adult human colon compared to four skin fibroblast cell lines to identify intestinal myofibroblast specific markers
2016-04-06 | E-GEOD-77474 | biostudies-arrayexpress
Project description:Skin and lung fibrosis in systemic sclerosis (SSc) is driven by myofibroblasts, alpha-smooth muscle actin (SMA) expressing cells that produce matrix as well as increase tension on surrounding tissues. Myofibroblast progenitors have been described to arise from a variety of cell types in murine fibrosis models, but relatively modest insight is available as to their source and differentiation in fibrotic human diseases. We utilize single cell RNA-sequencing to examine the transcriptome changes that occur in fibroblasts in SSc skin and during myofibroblast differentiation. We show that dermal myofibroblasts arise from an SFRP2/DPP4-expressing progenitor fibroblast population. In SSc skin, fibroblasts undergo global changes in gene expression, including SFRP2-expressing fibroblasts, which globally upregulate expression of markers, such as PRSS23 and THBS1. However, only a fraction of SSc fibroblasts differentiate into myofibroblasts, as shown by expression of additional markers, such as SFRP4 and FNDC1. These results indicate that myofibroblasts derive from a specific fibroblast subpopulation in SSc skin, that their differentiation proceeds in two stages and that other fibroblast populations also shift transcriptomes in SSc skin, suggesting a cytokine driven process. The myofibroblast transcriptome implicates upstream transcription factors that should help further unravel the drivers of myofibroblast differentiation.
2021-05-20 | GSE138669 | GEO
Project description:Early cardiac ageing: Phenotypic and transcriptional transitions in young to middle-aged mice
| PRJNA743067 | ENA