Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA258553 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1649430_1.fastq.gz | Fastqsanger.gz | |||
| SRR1649430_2.fastq.gz | Fastqsanger.gz | |||
| SRR1649431_1.fastq.gz | Fastqsanger.gz | |||
| SRR1649431_2.fastq.gz | Fastqsanger.gz | |||
| SRR1649426_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Forced expression of activated beta-catenin in mouse dermal fibroblasts is sufficient to cause spontaneous, progressive skin fibrosis in vivo. We generated triple-transgenic HoxB6CreERT/+; R26-YFP/+; CatnbΔex3/+ "activated beta-catenin" mice and double-transgenic HoxB6CreERT/+; R26-YFP/+ littermate control mice. We induced Cre activity (resulting in expression of activated beta-catenin in triple-transgenic mutant fetuses) by administering tamoxifen to the pregnant dam at embryonic day 16.5. The activated beta-catenin mice developed fibrotic skin, characterized by elevated collagen deposition and increased fibroblast proliferation. We performed RNA-sequencing to profile gene expression in the dermis of control and activated beta-catenin mutant mice with established skin fibrosis at 3 weeks of age.
2014-12-01 | GSE60569 | GEO
Project description:Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis. We have isolated the following populations of cells from mouse back skin by flow cytometry: 1A) GFP+ WT neonatal dermal fibroblasts, 1B) ItgA6+ WT neonatal epidermal keratinocytes, 2A) GFP+ WT telogen dermal fibroblasts, 2B) ItgA6+ WT telogen epidermal keratinocytes, 3A) GFP+ D2 transient activation (anagen) dermal fibroblasts, 3B) ItgA6+ D2 transient activation (anagen) epidermal keratinocytes, 4A) GFP+ D2 sustained activation (ectopic follicles) dermal fibroblasts, 4B) ItgA6+ D2 sustained activation (ectopic follicles) epidermal keratinocytes
2011-10-12 | E-GEOD-32966 | biostudies-arrayexpress
Project description:Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis.
2011-10-13 | GSE32966 | GEO
Project description:Dermal sheath (DS) shows potent hair inducing capability and high plasticity without leading to immuno rejection. A recent study showed a subset of DS cells, identified as hair follicle (HF) dermal stem cells, can be mobilized to regenerate DS, maintain/supply the cell number of dermal papilla (DP) and modulate hair type. However, it is unclear how Wnt/β-catenin signaling regulates DS cells behaviors. Here we report that activation of β-catenin in DS, to some extent, endows it with hair inducing ability, reprogramming HF epidermal cells to generate new outgrowth. The new formed dermal condensates (DC)/DP lying adjacent the outgrowth derives from DS and/or its progeny, and homeostasis of pre-existing HFs is disturbed. Additionally, progressive skin fibrosis is prominent in hypodermis, where the excessive activated fibroblasts at least partially originate from DS and/or its progeny. Gene expression analysis of purified DS cells revealed that 44% DC signature genes are regulated, most of which are up-regulated. We found elevated expression of several growth factors, including Noggin, Fgf7 and Fgf10, which were previously implicated in HF induction. In summary, we confirm the high plasticity of DS cells by in vivo assays and report a mechanism by which Wnt/β-catenin signaling controls DS cells behaviors.
2016-05-31 | GSE81615 | GEO
Project description:The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alpha‐catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that -catenin stabilization between E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.
2016-01-12 | GSE76751 | GEO
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
Project description:The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alphaâ??catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that ï?¢-catenin stabilization between E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases. The dermis was separated from back skin of PDGFRAeGFP postnatal pups (P2) by incubation with thermolysin (0.25 mg/ml) (Sigma T7902) overnight at 4° and further processed as previously described (Collins et al., 2011). Cells were labeled in PBS + 10% FBS TruStain fcX anti-mouse blocking buffer with the following antibodies: anti-mouse Ly-6A/E (Sca-1)-Alexa Fluor-700 17. Two populations of cells were collected in triplicate. The PDGFRaH2BeGFP/Sca1- and the PDGFRaH2BeGFP/Sca1+. RNA was isolated and prepared for microarray analysis and hybridized to Affymetrix MG430.2A arrays. C, digested in DMEM + 10% FBS containing 2.5 mg/mL collagenase I (Gibco 17100- 017), and further processed
2016-01-12 | E-GEOD-76751 | biostudies-arrayexpress
Project description:RNA-Seq of in vitro Beta-Catenin-Stabilized Mouse Dermal Fibroblasts
| PRJNA407357 | ENA
Project description:Dermal sheath (DS) shows potent hair inducing capability and high plasticity without leading to immuno rejection. A recent study showed a subset of DS cells, identified as hair follicle (HF) dermal stem cells, can be mobilized to regenerate DS, maintain/supply the cell number of dermal papilla (DP) and modulate hair type. However, it is unclear how Wnt/β-catenin signaling regulates DS cells behaviors. Here we report that activation of β-catenin in DS, to some extent, endows it with hair inducing ability, reprogramming HF epidermal cells to generate new outgrowth. The new formed dermal condensates (DC)/DP lying adjacent the outgrowth derives from DS and/or its progeny, and homeostasis of pre-existing HFs is disturbed. Additionally, progressive skin fibrosis is prominent in hypodermis, where the excessive activated fibroblasts at least partially originate from DS and/or its progeny. Gene expression analysis of purified DS cells revealed that 44% DC signature genes are regulated, most of which are up-regulated. We found elevated expression of several growth factors, including Noggin, Fgf7 and Fgf10, which were previously implicated in HF induction. In summary, we confirm the high plasticity of DS cells by in vivo assays and report a mechanism by which Wnt/β-catenin signaling controls DS cells behaviors. We prospectively isolated control and cÎex3 DS cells (YFP+ve CD34-ve ALP-ve ITGα8-ve cells) from P15 dorsal skins by FACS.
2016-05-31 | E-GEOD-81615 | biostudies-arrayexpress
Project description:Wnt/β-catenin is involved in every aspect of embryonic development and in the pathogenesis of many human diseases, and is also implicated in organ fibrosis. However, the role of β-catenin-mediated signaling on liver fibrosis remains unclear. To explore this issue, the effects of PRI-724, a selective inhibitor of the cAMP-response element-binding protein-binding protein (CBP)/β-catenin interaction, on liver fibrosis were examined using carbon tetrachloride (CCl4)- or bile duct ligation (BDL)-induced mouse liver fibrosis models. Following repetitive CCl4 administrations, the nuclear translocation of β-catenin was observed only in the non-parenchymal cells in the liver. PRI-724 treatment reduced the fibrosis induced by CCl4 or BDL, accompanied by the suppression of S100A4 expression, a CBP/β-catenin transcript. C-82, an active form of PRI-724, inhibited the activation of isolated primary mouse quiescent hepatic stellate cells (HSCs) and promoted cell death in culture-activated HSCs. During the fibrosis resolution period, an increase in F4/80+ CD11b+ and Ly6Clow CD11b+ macrophages was induced by CCl4 and was sustained for two weeks thereafter, even after having stopped CCl4 treatment. PRI-724 accelerated the resolution of CCl4-induced liver fibrosis, and this was accompanied by increased matrix metalloproteinase (MMP)-9, MMP-2, and MMP-8 expression in intrahepatic leukocytes. These results suggest that the inhibition of CBP/β-catenin suppresses liver fibrosis through the inhibition of HSCs activation, the induction of activated HSC death, and the production of MMPs from macrophages. Thus, targeting the CBP/β-catenin interaction may become a new therapeutic strategy in treating liver fibrosis. We used microarrays to detail the global change of gene expression by PRI-724 (C-82)-treatment in culture-activated murine hepatic stellate cells.
2018-09-30 | GSE73603 | GEO