RNA sequencing of Rictor-deficient epidermis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA551008 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9601033_1.fastq.gz | Fastqsanger.gz | |||
| SRR9601033_2.fastq.gz | Fastqsanger.gz | |||
| SRR9601034_1.fastq.gz | Fastqsanger.gz | |||
| SRR9601034_2.fastq.gz | Fastqsanger.gz | |||
| SRR9601035_1.fastq.gz | Fastqsanger.gz |
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Project description:Comparaison of the transcriptomes of WT and Foxp3-deficient regulatory T cells from the spleen of females that carried one mutant Foxp3∆EGFPiCre allele and a second competent Foxp3 allele (Foxp3RFP) that also directed the expression of the red fluorescent protein (RFP) . We then extended these studies to elucidate transcriptional pathways altered upon Rictor deletion in ∆Treg cells that may contribute to their improved regulatory function by analyzing the transcriptome of ∆Treg cells isolated from Foxp3∆EGFPiCre/+Rictor∆/∆ females.
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Project description:RNA sequencing data of mouse epidermis isolated from wild type and LAMA3-deficient mice Genetic, clinical and biochemical studies concurred to establish that integrity of the dermal-epidermal junction requires laminin 332, a particular subset of epithelial laminins. Laminin 332 is composed of three subunits, α3, β3 and γ2, encoded by the Lama3, Lamb3 and Lamc2 genes, respectively. In vivo functional analysis of laminin 332 in skin has been prevented because constitutive mutations of any one of the coding genes, either inherited in human or engineered in mice, cause junctional epidermolysis bullosa and early death. Consequently, it is still unknown whether and how laminin 332 contributes to skin homeostasis. To circumvent the problem, we have generated a mouse model in which disruption of the Lama3 gene is conditional and specifically induced in epidermal keratinocytes after birth. It causes a progressive depletion of laminin 332 in the skin of the mouse, which is compatible with life. To assess how laminin 332 supervises epidermal homeostasis, RNA was prepared from keratinocytes isolated from laminin 332-depleted skin and control animals (three each) to compare their gene expression profiles using RNA sequencing.
2021-02-18 | GSE146045 | GEO
Project description:ILK is essential for proper development of hair follicles, and for epidermal integrity and repair after injury. To better understand the pathways modulated by ILK in the epidermis, we compared the transcriptomes of ILK-deficient and -expressing epidermis using microarray analyses. Ilktm1Star (with floxed Ilk alleles) and Tg(KRT14-cre)1Amc/J mice were bred, and the resulting mice were bred again with Ilktm1Star mice, to generate animals heterozygos for the KRT14-cre transgene and either heterozygous (ILK-expressing) or homozygous (ILK-deficient) for the floxed Ilk alleles. The epidermis of 3 day-old animals was harvested and used to prepare RNA for the microarrays. The animals used were littermates. RNA from the epidermis of five ILK-deficient and five ILK-expressing mice were used.
2012-01-18 | E-GEOD-35129 | biostudies-arrayexpress
Project description:Skin microbiota affect systemic inflammation through mechanisms that have not been completely elucidated. We previously demonstrated that keratinocyte-specific IκBζ-deficient mice spontaneously develop autoimmune inflammation resembling human Sjögren syndrome. In this study, we examined how IκBζ-deficient epidermis dictates systemic autoimmune inflammation onset. To examine if IκBζ-deficient keratinocytes are susceptible to apoptotic stimuli in a steady state, we performed microarray analysis of untreated murine back epidermis. Data indicate that IκBζ-deficient epidermis is susceptible to environment antigens through apoptosis-related gene upregulation
2022-08-11 | GSE165515 | GEO
Project description:Nearly 50% of cutaneous melanomas carry activating mutations on the BRAF oncogene, and the combination of BRAF- and MEK-inhibitors (BRAF/MEKi) is frequently used for their clinical management. One major drawback of BRAF/MEKi targeted therapy is the rapid development of therapeutic resistance, which can occur via multiple mechanisms, including the metabolic rewiring of cancer cells that often involves the upregulation of mitochondrial bionergetics and NAD+ biosynthetic pathways. mTORC2 is a signaling complex that requires the presence of its essential RICTOR subunit to play its regulatory functions in cell growth and metabolism. mTORC2 is believed to play mostly pro-oncogenic roles in several tumor types, including melanoma. However, bioinformatics analysis of TCGA melanoma patients’ database revealed that low RICTOR levels in tumors correlate with an overall worse clinical outcome. GSEA analysis of low-RICTOR tumors evidenced also a gene expression signature suggestive of activation of mitochondrial energy producing pathways. On these bases, we have hypothesized that inhibition of mTORC2 activity may render BRAFV600E melanoma cells resistant to BRAFi/MEKi. We show here that RICTOR/mTORC2-deficient cells are intrinsically tolerant to BRAFi/MEKi, and anticipate the onset of resistance to BRAFi after sustained drug exposure both in vitro and in vivo, indicating that mTORC2 activity normally opposes the acquisition of targeted therapy resistance in BRAFV600E melanomas. Mechanistically, RICTOR-deficient cells show an enhanced mitochondrial respiratory potential and increased expression of nicotinamide phosphoribosyltransferase (NAMPT) protein, the rate-limiting enzyme of NAD+ salvage pathway, and pharmacological inhibition of these processes in RICTOR-deficient cells is sufficient to restore sensitivity to BRAFi. Thus, our work identifies a novel role for mTORC2 in favoring the responses of BRAF-mutated melanoma cells to targeted therapy, and suggest that the evaluation of the intratumor level of RICTOR may help to predict the responses of melanoma patients to these treatments.
2024-05-23 | PXD045346 | Pride
Project description:Background Main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF- mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to define in this context the specific role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit and regarded as an oncogenic driver in several tumor types, including MM. Methods After analyzing the TCGA MM patients’ database to explore both overall survival and molecular signatures as a function of intra-tumor RICTOR levels, we investigated the effects of RICTOR downregulation in BRAF V600E MM cell lines on their response to BRAF/MEKi in vitro. We performed a proteomic screening to identify proteins modulated by changes in RICTOR expression and Seahorse analysis to evaluate the effects of RICTOR depletion on mitochondrial respiration. The combination of BRAFi with drugs targeting proteins and processes emerged in the proteomic screening was carried out on RICTOR-deficient cells in vitro and in a xenograft setting in vivo. Results We found that low RICTOR levels in MM correlate with an overall worse clinical outcome. GSEA of low- RICTOR tumors revealed a gene expression signature suggestive of activation of the mitochondrial Electron Transport Chain (ETC) energy producing pathway. RICTOR-deficient BRAF V600E cells are intrinsically tolerant to BRAFi/MEKi and anticipate the onset of resistance to BRAFi upon prolonged drug exposure. In RICTOR- depleted cells, both mitochondrial respiration and expression of nicotinamide phosphoribosyltransferase (NAMPT) are enhanced, while their pharmacological inhibition restores sensitivity to BRAFi. Conclusions Our work unveils a novel tumor suppressing role for mTORC2 in the responses of BRAF V600E melanoma cells to targeted therapy and identifies the NAMPT-ETC axis as a potential therapeutic vulnerability of low- RICTOR tumors. Importantly, our findings support the concept that the evaluation of intra-tumor RICTOR levels in MM has a prognostic value, and may help predicting the response of patients to targeted therapy.
2024-06-22 | PXD050614 | Pride