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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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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]

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 | 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 [bleomycin]

2017-08-11 | GSE100212 | 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

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

2017-08-11 | GSE100250 | 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: Not available

| S-EPMC5491269 | biostudies-literature

Homo sapiens

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 [ECMs]

| PRJNA390302 | ENA

Mus musculus

| PRJNA390999 | 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

C4 Photosynthesis: Gene expression in mesophyll and bundle sheath cells of bundle sheath defective2 mutant

Project description:Zea mays is a C4 plant that utilizes two distinct cell types, mesophyll (M) and bundle sheath (BS), to cooperatively fix carbon. Regulation of M and BS cell differentiation is poorly understood. Here, we explore the transcriptional networks of M and BS cells by microarray analysis. The maize mutant bundle sheath defective2 lacks the accumulation of Rubisco small and large subunits (Roth et al 1996; Brutnell et al 1999) and cannot perform the Calvin Cycle (Smith et al 1998). Therefore, this mutant provides an opportunity to study M and BS cell differentiation in a perturbed BS background, potentially revealing regulons important to cell identity. M and BS cells were independently isolated from mutant and wild-type siblings. Transcriptional profiling was then performed in a cell specific manner between mutant and wild-type.

2018-04-30 | GSE13758 | GEO

CELL CONTRACTILITY AND AN ACTIN GRADIENT DRIVE POLAR ALIGNMENT OF FIBROBLASTS IN CONSTRAINED GEOMETRIES

Project description:When REF 2c cells were placed on circular micro-contact printed patterns, the boundary cells radially aligned over a period of 48 h. Video tracking of specific boundary and inner cells showed that this phenomenon was not caused by cells migrating towards or away from the periphery. Cell contractility, intercellular junctions, and cell-cell adhesion are required for radial alignment.

2020-04-07 | GSE148155 | GEO

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