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Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

ABSTRACT: Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

OTHER RELATED OMICS DATASETS IN: GSE100250GSE99999

PROVIDER: PRJNA391154 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5680560_1.fastq.gz	Fastqsanger.gz
	SRR5680560_2.fastq.gz	Fastqsanger.gz
	SRR5680570_1.fastq.gz	Fastqsanger.gz
	SRR5680570_2.fastq.gz	Fastqsanger.gz
	SRR5680580_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs [bleomycin]

Project description:Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention.

2017-08-11 | GSE100212 | GEO

Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs [ECMs]

2017-08-11 | GSE99999 | GEO

Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-08-11 | GSE100250 | GEO

Highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer

Project description:Discoidin domain-containing receptor 1 (DDR1) plays an important role in cancer progression. However, the DDR1 function in tumors is still elusive. We recently reported that DDR1 promoted collagen fiber alignment and formation of a physical barrier, which causes immune exclusion from tumors. We also demonstrated that our DDR1 ECD-targeting mAbs can disrupt collagen fiber alignment and increase T Cell infiltration in tumors. In this study, we humanized a DDR1 ECD-targeting mAb and showed significant antitumor efficacy in an immunocompetent mouse model. We determined the binding epitope using gene mutagenesis, hydrogen-deuterium exchange mass spectrometry (HDX-MS), and X-ray crystallography. Mechanistically, we showed that the humanized mAb inhibited DDR1 phosphorylation and, more importantly, blocked DDR1 shedding and disrupted a physical barrier formed by collagen fiber alignment in tumors. This study not only paves a pathway for development of PRTH-101 as a cancer therapeutic, but also broaden our understanding of the roles of DDR1 in modulation of collagen alignments in tumor extracellular matrix and tumor immune microenvironment.

2023-06-19 | PXD042971 | Pride

Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs.

| S-EPMC5491269 | biostudies-literature

Mus musculus

Project description:Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs [bleomycin]

| PRJNA390999 | ENA

Homo sapiens

| PRJNA390302 | ENA

MicroRNA profiling of human glioblastoma cell line U87 cell spheroids before and after migration on collagen

Project description:U87 cell spheroids were harvested from collagen on day 0 (no migration), or day 3 (extensive migration). The RNA extracted from these cells was used to identify microRNA alterations that occur during glioma cell line migration.

2010-01-28 | E-MEXP-2567 | biostudies-arrayexpress

Aligned Ancient Genomes

Project description:Alignment of publicly available ancient genomes to hg38

| PRJEB64654 | ENA

Producing Collagen Micro-stripes with Aligned Fibers for Cell Migration Assays.

Project description:IntroductionThe orientation of collagen fibers in native tissues plays an important role in cell signaling and mediates the progression of tumor cells in breast cancer by a contact guidance mechanism. Understanding how migration of epithelial cells is directed by the alignment of collagen fibers requires in vitro assays with standardized orientations of collagen fibers.MethodsTo address this issue, we produced micro-stripes with aligned collagen fibers using an easy-to-use and versatile approach based on the aspiration of a collagen solution within a microchannel. Glass coverslips were functionalized with a (3-aminopropyl)triethoxysilane/glutaraldehyde linkage to covalently anchor micro-stripes of aligned collagen fibers, whereas microchannels were functionalized with a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nonionic triblock polymer to prevent adhesion of the collagen micro-stripes.ResultsUsing this strategy, microchannels can be peeled off to expose micro-stripes of aligned collagen fibers without affecting their mechanical integrity. We used time-lapse confocal reflection microscopy to characterize the polymerization kinetics of collagen networks for different concentrations and the orientation of collagen fibers as a function of the microchannel width. Our results indicate a non-linear concentration dependence of the area of fluorescence, suggesting that the architecture of collagen networks is sensitive to small changes in concentration. We show the possibility to influence the collagen fibril coverage by adjusting the concentration of the collagen solution.ConclusionWe applied this novel approach to study the migration of epithelial cells, demonstrating that collagen micro-stripes with aligned fibers represent a valuable in-vitro assay for studying cell contact guidance mechanisms.

| S-EPMC6981333 | biostudies-literature

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