Project description:This SuperSeries is composed of the following subset Series:; GSE10726: Expression data from skin of epithelial activated beta-catenin mutant mouse embryo; GSE10727: Expression data from dermis of epithelial activated beta-catenin mutant mouse embryo; GSE10728: Expression data from epidermis of epithelial activated beta-catenin mutant mouse embryo Experiment Overall Design: Refer to individual Series
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.
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.
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
Project description:β-catenin signaling is required for hair follicle development, but it is unknown whether it is sufficient to activate expression of hair follicle genes in embryonic skin. To address this we profiled gene expression in dermis from E15.5 KRT14-Cre Ctnnb1(Ex3)fl/+ embryos carrying an activating mutation in epithelial beta-catenin, and control littermate embryos. Experiment Overall Design: Total dermal RNA from two KRT14-Cre Ctnnb1(Ex3)fl/+ and two control littermate E15.5 embryos was hybridized to Affymetrix GeneChip Mouse Genome MOE430 2.0 oligonucleotide microarrays. Experiment Overall Design: Appended below is Table S2: Full list of differentially expressed genes in KRT14-Cre Ctnnb1(Ex3)fl/+ mutant compared with control littermate dermis at E15.5, including normalization and filter parameters. Fold change, listed in the second column, gives the ratio of normalized mutant : control transcript levels.
Project description:We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their global gene expression profiles to define their differentially expressed regulators. To distinguish gene expression patterns that are shared by other developing epithelial/mesenchymal compartments in the embryo from those that pertain to the prostate stem cell niche, we also determine the global gene expression of epidermis and dermis of the same embryos. We identified a distinctive core of transcripts that were differentially regulated in the prostate stem cell niche. Our analysis indicates that several of the key transcriptional components that are likely to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Serbp1) and cell migration (e.g., Areb6 and Rreb1). Several of the promoter binding motifs that are enriched in the profiles are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. We also focused on defining ligand-receptor interactions that may be relevant in controlling signals in the stem cell niche and identified the Wnt/beta-catenin, ephrin, Notch, sonic hedgehog, FGF, TGF-beta and bone morphogenic signaling pathways as being of likely relevance in the prostate stem cell niches. Members of the integrins family including those that bind extracellular matrix proteins such as laminin and activate latent TGF-beta are also expressed in the prostate niche.development. Keywords: Differential gene expression Six biological replicate experiments were performed for UGE. Five biological replicate experiments were performed for UGM. Four biological replicate experiments were performed for Epidermis. Four biological replicate experiments were performed for Dermis.
Project description:β-catenin signaling is required for hair follicle development, but it is unknown whether it is sufficient to activate expression of hair follicle genes in embryonic skin. To address this we profiled gene expression in epidermis from E15.5 KRT14-Cre Ctnnb1(Ex3)fl/+ embryos carrying an activating mutation in epithelial beta-catenin, and control littermate embryos. Experiment Overall Design: Total epidermal RNA from two KRT14-Cre Ctnnb1(Ex3)fl/+ and two control littermate E15.5 embryos was hybridized to Affymetrix GeneChip Mouse Genome MOE430 2.0 oligonucleotide microarrays. Experiment Overall Design: Appended below is Table S1: Full list of differentially expressed genes in KRT14-Cre Ctnnb1(Ex3)fl/+ mutant compared with control littermate epidermis at E15.5, including normalization and filter parameters. Fold change, listed in the second column, gives the ratio of normalized control : mutant transcript levels.