Engrailed 1 coordinates cytoskeletal re-organization to induce myofibroblast differentiation
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ABSTRACT:
PROVIDER: PRJNA730706 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14574936_1.fastq.gz | Fastqsanger.gz | |||
| SRR14574936_2.fastq.gz | Fastqsanger.gz | |||
| SRR14574937_1.fastq.gz | Fastqsanger.gz | |||
| SRR14574937_2.fastq.gz | Fastqsanger.gz | |||
| SRR14574938_1.fastq.gz | Fastqsanger.gz |
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Project description:Engrailed 1 coordinates cytoskeletal re-organization to induce myofibroblast differentiation
| PRJNA730572 | ENA
Project description:Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases including systemic sclerosis. Here we show that Engrailed 1 (EN1) is re-expressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and, in turn, EN1 mediates the pro-fibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a pro-fibrotic gene expression profile functionally related to the cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP-transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the re-organization of cytoskeleton during myofibroblast differentiation both in standard fibroblast culture systems and in in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis.
2021-05-18 | GSE174580 | GEO
Project description:Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases including systemic sclerosis. Here we show that Engrailed 1 (EN1) is re-expressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and, in turn, EN1 mediates the pro-fibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a pro-fibrotic gene expression profile functionally related to the cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP-transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the re-organization of cytoskeleton during myofibroblast differentiation both in standard fibroblast culture systems and in in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis.
2021-05-19 | GSE174598 | GEO
Project description:Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) is reexpressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and in turn, EN1 mediates the profibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a profibrotic gene expression profile functionally related to cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the reorganization of cytoskeleton during myofibroblast differentiation, in both standard fibroblast culture systems and in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis.
| S-EPMC8288503 | biostudies-literature
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:We sought to identify genes necessary to induce cytoskeletal change in B cells. Using gene expression microarray, we compared B cells stimulated with Interleukin-4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility, tight aggregates, and extensive microvilli with B cells stimulated with lipopolysaccharide (LPS) that lack these cytoskeletal changes.
2017-03-21 | GSE96813 | GEO
Project description:Transcriptional profiling of drosophila embryos (0-14h collection) comparing control wild type embryos with embryos double heterozygous for Engrailed and GooseberryNeuro Two conditions experiment, Wild Type vs. Double heterezygous Engrailed GooseberryNeuro. Biological replicates: 3 control, 3 mutant conditions, independently selected. Triplicate per array
2014-01-01 | E-GEOD-46628 | biostudies-arrayexpress
Project description:Transcriptional profiling of drosophila embryos (0-14h collection) comparing embryos double heterozygous for Engrailed and GooseberryNeuro with control wild type embryos
2014-01-01 | GSE46628 | GEO
Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis. RNA-seq data for differentially expressed genes in the SNpc of En1+/- mice, En2 infused mice and 6-OHDA/En2 injection experiments.
2015-09-24 | E-GEOD-72321 | biostudies-arrayexpress
Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis.
2015-09-24 | GSE72321 | GEO