Alternative mRNA splicing in human epidermal differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201094 | GEO | 2023/01/02
REPOSITORIES: GEO
Similar Datasets
Project description:The aim of this study was to establish a deeply sequenced transcriptome at multiple timepoints during the differentiation of human epidermal keratinocytes from the progenitor state (d0). These transcriptomes were then assembled in order to discover novel genes and transcriptional events that are dynamically regulated during terminal differentiation of a human somatic tissue. Paired-end RNA sequencing was performed on primary human keratinocytes at three timepoints during calcium-induced epidermal differentiation.
2012-02-02 | E-GEOD-35468 | biostudies-arrayexpress
Project description:The aim of this study was to establish a deeply sequenced transcriptome at multiple timepoints during the differentiation of human epidermal keratinocytes from the progenitor state (d0). These transcriptomes were then assembled in order to discover novel genes and transcriptional events that are dynamically regulated during terminal differentiation of a human somatic tissue.
2012-02-02 | GSE35468 | GEO
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>
| phs001737 | dbGaP
Project description:We discovered that glucose directly bind to DDX21, induced the conformation change of the proteins and inhibit its helicase activity. Glucose also inhibits the dimerization of DDX21, re-localize DDX21 from nucleolus to nucleoplasm and reassemble DDX21 to RNA splicing complex. DDX21 is essential for epidermal differentiation while with normal glucose condition, DDX21 was re-localized from nucleolus to nucleoplasm, bind to splicing factors and mRNA introns more to regulate splicing of key differentiation factors and promote epidermal differentiation.
2023-01-05 | PXD028561 | Pride
Project description:The incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer. In this project we used SOLiD next generation sequencing to characterize gene expression profiles in normal human epidermal keratinocytes (NHEKs) and cSCC cell lines. Total RNAs from normal human epidermal keratinocytes (NHEKs) (n=4) and cSCC cell lines (n=8) were extracted. The samples were sequenced using SOLiD next generation sequencing.
2015-08-27 | E-GEOD-66412 | biostudies-arrayexpress
Project description:Numerous long non-coding RNAs (lncRNAs) were shown to have functional impact on cellular processes, such as human epidermal homeostasis, but for only a few the mode of action has been elucidated. Here, we report that lncRNA LINC00941 controls keratinocyte differentiation on a global level through association with the MTA2/NuRD complex, one of the major chromatin remodelers in cells. LINC00941 was found to interact with NuRD-associated MTA2, suppressing the expression of the transcription factor EGR3, a regulator of epidermal differentiation. Both LINC00941 and the MTA2/NuRD complex are enriched in non-differentiated keratinocytes and repress the expression of differentiation genes through epigenetic silencing of EGR3, consequentially preventing premature differentiation of human progenitor cells.
2024-04-08 | PXD043838 | Pride
Project description:RNA-seq was used to define the role of MAB21L4 in epidermal differentiation by placing primary human keratinocytes transduced to overexpress MAB21L4 onto human dermis and grown for three days at the air-liquid interface to generate organotypic skin tissue.
2022-06-24 | GSE190865 | GEO
Project description:The specific functional features of the epidermal keratinocytes are determined by the activity of many genes. The aim of the project was to characterize the role of HSPA2, a member of the HSPA chaperone family (HSP70), in human epidermal keratinocytes. The inactivation of the HSPA2 gene in the HaCaT line of spontaneously immortalized epidermal keratinocytes was performed by CRISPR/Cas9 gene editing system. Next, the effect of modifications on the transcriptomic profile of cells growing in a three-dimensional model of reconstructed human epidermis in vitro was investigated. The cells were grown at air-liquid interface culture on collagen-fibroblast matrix to achieve maximal level of HaCaT differentiation in RHE system.
2023-09-25 | E-MTAB-13166 | biostudies-arrayexpress
Project description:Progenitor cells at the basal layer of skin epidermis play an essential role in maintaining tissue homeostasis and enhancing wound repair in skin. The proliferation, differentiation, and cell death of epidermal progenitor cells have to be delicately regulated, as deregulation of this process can lead to many skin diseases, including skin cancers. However, the underlying molecular mechanisms involved in skin homeostasis remain poorly defined. In this study, with quantitative proteomics approach, we identified an important interaction between KDF1 (Keratinocyte Differentiation Factor 1) and IKKα (IκB kinase α) in differentiating skin keratinocytes. Ablation of either KDF1 or IKKα in mice leads to similar but striking abnormalities in skin development, particularly in skin epidermal differentiation. With biochemical and mouse genetics approach, we further demonstrate that the interaction of IKKα and KDF1 is essential for epidermal differentiation. To probe deeper into the mechanisms, we find that KDF1 associates with a deubiquitinating protease, USP7 (Ubiquitin Specific Peptidase 7), and KDF1 can regulate skin differentiation through deubiquitination and stabilization of IKKα. Taken together, our study unravels an important molecular mechanism underlying skin tissue homeostasis and epidermal differentiation.
2020-05-13 | PXD015673 | Pride
Project description:An essential function of the human epidermis is the maintenance of a protective barrier against the environment. As a consequence, keratinocytes, which make up this layer of the skin, undergo an elaborate process of self-renewal, terminal differentiation and cell death. Misregulation of these processes can lead to several human diseases including psoriasis and basal cell and squamous cell carcinomas. To identify novel regulators of keratinocyte differentiation, a cell-based screen of small molecule libraries was carried out for molecules that induce terminal differentiation of normal human epidermal keratinocytes (NHEKs). One class of molecules was identified, the 2-(3,4,5-trimethoxy-phenylamino)-pyrrolo[2,3-d]pyrimidines, which were shown to induce differentiation of epidermal progenitor cells to terminally differentiated keratinocytes. These molecules serve as useful mechanistic probes of the cellular differentiation programs that regulate the formation and homeostasis of the epidermis, and may lead to novel therapeutic approaches for the treatment of skin hyperproliferative disorders. Keywords: time course of compound treatment
2007-02-07 | GSE6932 | GEO