ABSTRACT: miRNA expression data from cultivated Human Thymic Epithelial Cells (hTECs) in comparison with cultivated Human Epidermal derived Keratinocytes (hEKs)
Project description:Expression data from cultivated Human Thymic Epithelial Cells (hTECs) in comparison with cultivated Human Epidermal derived Keratinocytes (hEKs)
Project description:Genome-wide mRNA and miRNA expression data from different populations of human thymic epithelial cells (hTECs) compared to human epidermal derived keratinocytes
Project description:The thymic epithelium and the epidermis display many common features despite their different structure, function and embryonic origin. We used microarrays to uncover differences and similarities in the miRNA expression profile of hTECs and hEKs and investigate their significance for the peculiar organization of the thymic structure.
Project description:Thymic epithelial cells (TECs) are essential for thymopoiesis and form a complex three-dimensional network, the organization of which is strikingly different from other epithelia. Interestingly, TECs express simple epithelia keratins in the cortex, stratified epithelia keratins in the medulla and epidermal differentiation markers in Hassall's bodies. Here we investigate the relationship between thymic epithelium and epidermal differentiation and show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured and cloned using conditions developed for epidermal cell therapy in human. Clonogenic TECs conserve a thymic identity and the capacity to integrate in a thymic epithelial network, but they acquire new functionalities when exposed to an inductive skin microenvironment, permanently adopting the fate of hair follicle multipotent stem cells. This change in fate, maintained over time in serial transplantation, correlates with a down-regulation of transcription factors important for thymic identity, and an up-regulation of epidermal markers. Consequently, the TECs’ capacity to integrate in a thymic epithelial network is altered or even lost. Our results demonstrate that the thymus contains a population of holoclone-like epithelial cells that can function as bona fide multipotent keratinocyte stem cells, and that microenvironmental cues are sufficient to re-direct epithelial-cell fate, allowing crossing of primitive germ layer boundaries from endoderm to ectoderm. Keywords: Cell type comparison
Project description:We established a culture method of human keratinocytes from the bulge region of a plucked hair follicle, that contains multipotent epithelial stem cells with high proliferative potential. Using our method, keratinocyte cultures were successfully obtained from all subjects without invasive skin biopsies. We compared the gene expression profiles between the cultured keratinocytes derived from human hair-follicle-bulge (bulge–derived keratinocytes; BDKs) and neonatal human epidermal keratinocytes (NHEKs), and between BDKs from donors with atopic dermatitis and non-atopic controls using microarray analysis. Keywords: expressin profiling
Project description:<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate (EEC) syndrome. Underlying molecular mechanism of these mutations however remain unclear. Here we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify an unreported disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>
Project description:We identified pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. The biological function of these miRNAs in human epidermal keratinocytes or fibroblasts during wound repair remains unclear. To study the genes regulated by miR-96-5p, miR-218-5p, miR-424-5p, miR-450b-5p, miR-516b-5p or miR-7704, we transfected miRNA mimics into human primary epidermal keratinocytes or fibroblasts to overexpress respective miRNA expression. We performed a global transcriptome analysis of keratinocytes or fibroblasts upon miRNA overexpression using Affymetrix arrays.
