Project description:Genetic investigation in Mendelian skin disorders featuring generalized or localized skin scaling and redness, known as the ichthyoses, has revealed novel pathways relevant to epidermal integrity, barrier function, and desquamation. Here we show that a recurrent de novo missense variant in EMP2 (epithelial membrane protein 2), which encodes a cell surface tetraspan protein in the growth-arrest specific 3 (GAS3)/peripheral myelin protein 22 (PMP22) family, is associated with a previously undescribed Mendelian disorder in the progressive symmetric erythrokeratoderma spectrum. The disorder features severely thickened, red and scaly skin at sites of wound healing or repetitive movement including on the face, genitals, flexural areas, and the palms and soles. EMP2 has previously been shown to directly associate with focal adhesion kinase (FAK), which links cell junction forces to signaling pathways relevant to proliferation, migration, and wound healing. Using single-cell spatial transcriptomics in affected tissue, we discovered ectopic suprabasal activation of signaling pathways downstream of receptor tyrosine kinases including epidermal growth factor receptor (EGFR), which we confirmed with Western blotting in affected cells, supporting a gain-of-function mechanism for mutant EMP2. Remarkably, treatment with erlotinib, an EGFR inhibitor, led to marked clinical improvement underscoring the key role of EMP2 in epidermal differentiation and proliferation.
Project description:These data were used in the spatial transcriptomics analysis of the article titled \\"Single-Cell and Spatial Transcriptomics Analysis of Human Adrenal Aging\\".
Project description:To investigate spatial heterogeneities in the axolotl forebrain, a coronal section of it was obtained for spatial transcriptomics using Visium V1.
Project description:Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1).
Project description:Spatial organization of different cell types within prenatal skin across various anatomical sites is not well understood. To address this, here we have generated spatial transcriptomics data from prenatal facial and abdominal skin obtained from a donor at 10 post conception weeks. This in combination with our prenatal skin scRNA-seq dataset has helped us map the location of various identified cell types.
Project description:Identification of cell types in the interphase between muscle and tendon by Visium Spatial Transcriptomics of four human semitendinous muscle-tendon biopsies. Cell types identified by single nuclei RNA seq on similar tissue were localized in situ with the use of Spatial Transcriptomics.
Project description:This data is from healthy skin tissue and has been used as a reference to compare diseased datasets. The dataset is from experiments of spatial transcriptomics.
Project description:These samples are part of a study investigating cancer cell plasticity in colorectal cancer metastasis. Spatial transcriptomics was performed using 10x Genomics Visium on colorectal cancer liver metastatic patient samples.