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Transcriptomic analysis of pro-invasive fibroblasts activation short term response

ABSTRACT: The effect at short term (48 hours) of leukemia inhibitory factor (LIF), TGFβ or TGFβ + anti-Lif stimulation on the human primary dermal fibroblast (hDF) transcriptome was analyzed by whole genome microarray expression profiling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81996 | GEO | 2016/12/06

SECONDARY ACCESSION(S): PRJNA323597

REPOSITORIES: GEO

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Transcriptomic analysis of pro-invasive fibroblasts activation long term response

Project description:The effect at long term (15 days) of leukemia inhibitory factor (LIF), TGFβ or TGFβ + anti-Lif stimulation on the human primary dermal fibroblast (hDF) transcriptome was analyzed by whole genome microarray expression profiling.

2016-12-06 | GSE81997 | GEO

Differentially transcribed miRNAs in stress-induced premature senecence (SIPS)

Project description:Detection of senescence-associated miRNAs differentially transcribed during early (D7) and late stages (D21) of human dermal fibroblast (HDF) senescence

2018-06-08 | GSE95354 | GEO

Whole-genome microarray analysis was performed on cells treated with 5 μM dTAT for 1h

Project description:Analysis of the impacto of dTAT treatment on primary human dermal flibroblast at the gene expression level. Results show that dTAT cytosolic penetration has a minimal impact on mRNA expression and that cells rapidly recover from treatment with dTAT. Primary Human dermal Fibroblast (HDF) were treated with dTAT (5µM) for 1h. Total RNA was harvested from HDF cells immediately, 1h or 24h after treatment.

2014-05-09 | E-GEOD-57427 | biostudies-arrayexpress

Targeting DDR1 and DDR2 overcomes matrix-mediated melanoma cell adaptation to BRAF-targeted therapy

Project description:To investigate the contribution of fibroblast-derived extracellular matrices (ECMs) to the resistance to targeted therapies in BRAF-mutated melanoma cells, we generated native-like 3D ECMs from human primary fibroblasts obtained from healthy individuals or melanoma patients. Cell-derived matrices from human dermal fibroblasts (HDF), skin melanoma associated fibroblasts (MAF) and two different lymph node fibroblast reticular cells (FRC) were denuded of cells and their composition was analyzed by mass spectrometry.

2021-11-12 | PXD026645 | Pride

Correlating functional heterogeneity of human dermal fibroblasts with differences in gene expression

Project description:Recent work has identified markers of fibroblast heterogeneity in human dermis. Transforming growth factor-β1 (TGF-β1) promotes fibroblast-to-myofibroblast differentiation, characterised by the expression of α-smooth muscle actin (α-SMA). Human dermal fibroblasts (hDF), treated with TGF-β1, were assayed for differentiation, proliferation and cell shape using the Operetta imaging system. One donor hDF, derived from female 64-year-old breast skin, expressed decreased levels of α-SMA protein. The gene expression profile of this donor hDF was determined using the Agilent microarray system. Four gene candidates (Asporin, ASPN; C-X-C motif chemokine ligand 1, CXCL1; Insulin-like growth factor 1, IGF1; and Wnt family member 4, WNT4) were chosen based on expression values and validated by TaqMan qPCR. Successful knockdown of IGF1 and WNT4 was achieved using MISSION shRNA-based lentiviral treatment. Fibroblast IGF1 knockdown (shIGF1) increased α-SMA mRNA and protein expression; no effect was seen with fibroblast WNT4 knockdown (shWNT4). Here I have characterised hDF phenotype and gene expression with regard to population heterogeneity. This work highlights the role of IGF-1 signalling on α-SMA expression and dermal fibroblast fate. Targeting IGF-1 signalling could provide therapeutic benefit for skin disorders involving aberrant wound healing and excessive fibrosis.

2021-01-01 | GSE140962 | GEO

IL11 is elevated in systemic sclerosis and IL11-dependent ERK signaling is needed for the profibrotic activity of TGFβ in dermal fibroblasts

Project description:Objectives: Interleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 is mechanistically linked with human dermal fibroblast (HDF) activation. Methods: We measured serum IL11 levels in healthy volunteers and patients with early diffuse SSc and manipulated IL11 signalling in HDFs using gain- and loss-of-function approaches. Results: In patients with SSc, serum IL11 levels are elevated as compared to healthy controls. Transforming growth factor beta (TGFβ) isoforms 1, 2 or 3 induced IL11 secretion from HDFs, which highly express IL11RA and the gp130 co-receptor, suggestive of an autocrine loop of IL11 activity in HDFs. IL11 consistently and robustly stimulated ERK activation in HDFs and resulted in HDF-to-myofibroblast transformation. IL11 induced STAT phosphorylation to a lesser extent than ERK and only at high IL11 concentrations. IL11-stimulated ERK activation and fibrosis phenotypes were absent in skin fibroblasts from patients with homozygous loss-of-function mutation in IL11RA. Inhibition of IL11 signaling using either a neutralizing antibody against IL11 or siRNA against IL11RA reduced TGFβ-induced HDF proliferation, matrix production and cell migration, which was phenocopied by pharmacologic inhibition of ERK activity. Conclusions: These data reveal an important contribution of IL11-related ERK activity for TGFβ-stimulated fibrosis phenotypes in HDFs and suggest IL11 as a potential therapeutic target in SSc.

2021-02-22 | GSE162966 | GEO

Whole transcriptome microarray analysis of human cells treated with the endosomolytic D-amino acid CPP, D-dfTAT

Project description:Analysis of the impact of D-dTAT treatment on primary human dermal flibroblast (HDF) and immortalized fibroblast cells (MCH58) at the transcriptome level. Results show that D-dTAT cytosolic penetration dysregulation of mRNA expression compared to dfTAT treated and untreated cells.

2016-12-30 | GSE90575 | GEO

Transcriptomic analysis of pro-invasive fibroblasts activation short and long term response

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

2016-12-04 | GSE81998 | GEO

EphB2 receptor promotes dermal fibrosis in systemic sclerosis

Project description:Objectives: Eph/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc). Methods: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting EphB2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward signaling in bleomycin-induced dermal fibrosis. In vitro studies were performed on dermal fibroblasts from SSc patients and healthy controls, which was followed by in vivo analysis of fibroblast-specific EphB2 deficient mice. Results: Expression of EphB2 is upregulated in SSc skin tissue and explanted SSc dermal fibroblasts compared to healthy controls. EphB2 expression is elevated in two animal models of dermal fibrosis. In mice, EphB2 drives dermal fibrosis in both the bleomycin and the Tsk1/+ models of skin fibrosis. EphB2 forward signaling is a critical mediator of dermal fibrosis. Transforming growth factor-β (TGFβ) cytokines upregulate EphB2 in dermal fibroblasts via non-canonical TGFβ/SMAD signaling and silencing EphB2 in dermal fibroblasts is sufficient to dampen TGFβ-induced fibroblast-to-myofibroblast differentiation. Moreover, mice with fibroblast-specific deletion of EphB2 showed impaired fibroblast-to-myofibroblast differentiation and reduced skin fibrosis upon bleomycin challenge. Conclusion: Our data implicate EphB2 overexpression and kinase-mediated forward signaling in the development of dermal fibrosis in SSc. EphB2 thus represents a potential new therapeutic target for SSc.

2024-04-10 | GSE253089 | GEO

Gene expression analysis of human fetal pancreatic niche cell lines: Wk17.5h and Wk20.1

Project description:We derived cell lines from the human pancreatic niche from different sites during different temporal stages of fetal development when beta cells are differentiating and maturing. This screen uncovered differences between the human pancreatic niche at fetal week 17.5 head of pancreas(Wk17.5h) and 20.1 doudeum (Wk 20.1) and control cell line human dermal fibroblast(HDF), illustrating a temporally changing, developmentally significant microenvironment.

2019-02-01 | GSE102877 | GEO

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