Project description:The type I intermediate filament keratin 16 (Krt16 gene; K16 protein) is constitutively expressed in ectoderm-derived appendages and volar palmar/plantar epidermis, and is otherwise inducibly expressed in non-volar epidermis when skin epithelia are under stress. Mutations at the (human) KRT16 locus can cause pachyonychia congenita (PC) and focal non-epidermolytic palmoplantar keratoderma (PPK), which each entail painful calluses on palmar and/or plantar skin. Krt16 null mice develop footpad lesions that mimic several aspects of PC-associated PPK and FNEPPK, including hypoactive Keap1-Nrf2 signaling and elevated expression of skin barrier homeostasis genes and Danger Associated Molecular Patterns (DAMPs). This provides a unique opportunity to understand the intricacies of PPK and devise effective therapies (see Lessard and Coulombe, J. Invest. Dermatol. 2012; Lessard et al. PNAS (USA) 2013; Kerns et al. J. Clin. Invest. 2016; Kerns et al., J. Invest. Dermatol. 2018; Zieman and Coulombe Exp. Dermatol. 2018). Here, we report on insight gained from a genome-wide analysis of gene expression in PPK-like lesions of Krt16 null mice. In this dataset, we include expression data obtained from Krt16 null paw skin lesions and WT littermate controls (C57Bl/6 strain background) at two months of age.
Project description:Investigation of the transcriptomic differences that occur in psoriatic skin lesions, compared to non arthritic skin or non-lesion arthritic skin.
Project description:In this study, a comprehensive assessment of human miRNA was performed on leprosy skin lesions using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-eight samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified differentially expressed miRNAs [Fold Change (FC)≥2.0, p<0.05] in disease lesions versus healthy controls or between them. Some of these miRNAs were validated by RT-PCR.
Project description:SCLE is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythematosus, the pathological mechanism of SCLE has been poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing of SCLE skin lesions and integrated with single cell RNA sequencing data of healthy skin. Our results firstly demonstrated that immune cells such as T, B, macrophage/DC and NK cells increased in the skin lesions of SCLE patients. Secondly, through sub-clustering analysis, GO enrichment analysis and cell communication analysis, we revealed that stromal cells such as keratinocytes and fibroblasts in skin lesions of SCLE enhanced chemotactic function for recruiting immune cells. Importantly, we found widespread high expression of interferon-related genes across almost all cell subtypes in SCLE lesions. Additionally, we revealed a general augmentation in lymphocyte subtypes and an increase in inflammatory myeloid cells such as M1 macrophages and pDC in SCLE lesions. In addition to secreting autoreactive antibodies, B cell subsets were verified to assist local immune responses in SCLE lesions. In conclusion, our investigation provides a comprehensive description of skin lesions in SCLE and suggests a range of potential therapeutic targets.
Project description:Here we report the data generated by short-read sequencing of mRNA (polyA) isolated from granuloma annulare and leprosy skin lesions. Our main aim was to identify putative mRNA biomarkers for distinguishing leprosy from other differential diagnoses. Additionally, we also explored the distinction between MB and PB by using differential expression analysis as well as training a penalized logistic regression to select important features. Our results showed that few genes are enough to differentiate leprosy lesions, including paucibacillary cases, from other morphological and histopathological similar skin diseases. Some of these genes have been replicated in a larger and more heterogeneous sample with RT-qPCR, validating their classification potential. We also suggest important novel gene candidates to improve our understanding of molecular differences between MB and PB lesions, which could either pinpoint new pathways and targets for host-based specialized adjuvant treatment for leprosy. Finally, this dataset has been used to explore the relationship between cornification and keratinocyte-related genes and TGFB-mediated epithelial-mesenchymal transition (EMT), which could indicate that in skin, M. leprae could be de-differentiating, directly or indirectly, other cell types into a progenitor/stem-like phenotype, facilitating mycobacterial survival and migration within the host. Alternatively, this could highlight which pathways are activated during granuloma formation and/or skin barrier assembly/disassembly.
Project description:Psoriasis is a chronic inflammatory skin disease characterized by marked proliferation of keratinocytes leading to pronounced epidermal hyperplasia, elongation of rete ridges and hyperkeratosis. The most common form of psoriasis, chronic plaque psoriasis (Psoriasis vulgaris), involves relatively stable occurrence and progression of sharply demarcated lesions, usually on the trunk and extremities, which share a combination of trademark histological features, including tortuous and dilated dermal capillaries, loss of the epidermal granular layer, and accumulation of neutrophils beneath parakeratotic scale. In this study, whole-genome transcriptional profiling was used to characterize gene expression in 4 lesional and uninvolved skin samples obtained from patients with stable chronic plaque psoriasis. Skin mRNA expression was analysed by microarray. Four individuals with chronic plaque psoriasis were enrolled. 6 mm punch biopsies were obtained under local anaesthesia (lidocaine) from uninvolved skin and a target plaque.
Project description:This study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of 61 histopathologically diagnosed Keratinocytic skin lesions (KSLs), including pre-malignant actinic keratosis (AK) and Bowen's disease (BD), and invasive cutaneous squamous cell carcinoma (cSCC)as well as matched normal stratum corneum samples collected from 26 patients.
Project description:In the absence of p63 expression, the epidermis fails to commit to stratification, resulting in aborted skin development. In this study, gene expression profiles of E18.5 p63 null and wt skin, were compared in an effort to identify genes that are directly or indirectly regulated by p63. Keywords: Genetically modified mice
Project description:This study was carried out to evaluate the changes that occur in the skin after the development of cutaneous leishmaniasis, aiming at a comprehensive understanding of immune pathways and biological functions activated in lesions caused by L. braziliensis. This analysis was conducted on 8 skin ulcers from patients infected with L. braziliensis. The patients selected for the gene expression analysis had recent L. braziliensis infection that had not yet been treated. 8 controls samples are skin biopsies from healthy donors (non-infected).