Single-Nucleus Chromatin Accessibility Identifies a Critical Role for TWIST1 in IPF Myofibroblast Activity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883741 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Multiomic single-cell analyses on human IPF lungs identify a global opening of TWIST1 and other E-box motifs in IPF myofibroblasts, with in vivo murine models confirming a critical regulatory function for TWIST1 in IPF myofibroblast activity.
2023-05-04 | GSE214085 | GEO
Project description:Non-fibrotic central regions of IPF lungs demonstrate massive dysregulated gene expression involving enhanced T-cell differentiation, pulmonary fibrosis idiopathic, and wound healing pathways. Enhancement of myofibroblast features without apparent extra-cellular matrix deposition in the central non-fibrotic region of IPF lungs renders a window for cell-based molecular targeting therapy.
2022-05-31 | GSE199949 | GEO
Project description:Background: Mechanistic target of rapamycin (mTOR) is a nodal serine/threonine protein kinase critical for the control of fundamental cellular processes. Dysregulated mTOR signalling has been shown in cancer, COPD and idiopathic pulmonary fibrosis (IPF). mTOR forms the catalytic subunit of 2 protein complexes: mTORC1 and mTORC2 which differ in upstream inputs, downstream effects and sensitivity to the allosteric inhibitor rapamycin. Aim: To compare the effects of the mTORC1 inhibitor rapamycin with an ATP-competitive inhibitor of mTORC1/2, AZD8055, on TGFβ1 induced transcriptional responses during myofibroblast differentiation by RNA-Seq analysis. Methods: Primary human lung fibroblasts were treated with TGFβ1 for 24h to induce myofibroblast differentiation and extra cellular matrix (ECM) production in the presence of rapamycin or AZD8055. Fibroblasts were also treated with rapamycin or AZD8055 without TGFβ1. Total mRNA was analysed by RNA-Seq. Results: On a global transcriptomic level, TGFβ1 significantly affected the expression of ~4,200 genes by more than 1.5 fold, of which ~1,100 changes were reversed by pan-mTORC1/2 inhibition, while being insensitive to rapamycin. Only 15 gene changes were reversed exclusively by rapamycin. Analysis of the rapamycin-insensitive, mTOR sensitive myofibroblast transcriptome revealed ECM-receptor interaction, metabolism and actin cytoskeleton regulation as major affected pathways. Conclusions: Our data support the conclusion that therapeutic approaches aimed at interfering with TGFb1 induced myofibroblast differentiation and ECM production require dual mTOR1/2 inhibition and may, in part, explain the lack of clinical efficacy of everolimus in the context of IPF.
2019-05-01 | GSE102674 | GEO
Project description:The Fibroblastic Focus (FF) is a lesion typical of Idiopathic Pulmonary Fibrosis (IPF). It is the site of myofibroblast accumulation and extracellular matrix (ECM) production. The molecular composition and function of the FF and surrounding tissue remain undefined. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogate the FF, adjacent mature scar tissue, and adjacent alveoli in 6 IPF specimens. To serve as a control, we perform LCM-MS on alveoli from 6 non-fibrotic controls.
2022-08-31 | PXD029341 | Pride
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:Viruses in acute exacerbations of idiopathic pulmonary fibrosis Keywords: viral detection BAL from patients with acute exacerbations of IPF and stable IPF were hybridized to a pan-viral cDNA microarray to evaluate the presence of virus during these episodes
2011-03-03 | E-GEOD-27578 | biostudies-arrayexpress
Project description:To compare the gene expression changes in IPF and normal lung tissues. 4 IPF and 4 Normal samples
2012-06-29 | E-GEOD-35145 | biostudies-arrayexpress
Project description:TWIST1 is known to play a role in the metastatic progression of melanoma. However, the range of TWIST1 targets is poorly charachterized. Here microarray analysis was used to define the TWIST1 regulated transcriptome in the human melanoma cell line WM793.
2019-04-03 | GSE128955 | GEO