Ontology highlight
ABSTRACT:
PROVIDER: PRJNA937388 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Autosomal recessive congenital ichthyosis (ARCI) is a group of rare inherited skin disorders characterized by remarkable hyperkeratosis. Transglutaminase 1 (TGM1) mutations have been reported to be involved in four different phenotypes of ARCI, including lamellar ichthyosis (LI), non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit ichthyosis (BSI), and self-improving collodion ichthyosis (SICI) according to the clinical presentation and histopathology. TGM1 has been found as a defective gene in a large amount of patients with LI and some patients with NBCIE, BSI and SICI. To further understand the effect of TGM1 mutations in epidermal cells development, we performed the transcriptome analysis of HEK293T and HaCaT cells transfected with TGM1 shRNA, TGM1 wild-type and mutant clones. The transcriptomic analysis revealed the effects of TGM1 on cell-cell interaction by suppressing genes involved in the gap junctions, tight junctions and desmosomes. These findings suggested that the TGM1 deficiency disturbed the balance of keratinocytes proliferation and differentiation processes and impaired the epithelial barrier function. The results provided the basis for further understanding on the etiology of ARCI. To explore the functional impacts on some of the TGM1mutations identified, we cloned and transfected the TGM1 wild type and mutant clones into HEK293T and HaCaT cells. R142C and R348X sequence mutations observed in ARCI (Autosomal recessive congenital ichthyosis) patients were generated. The shRNA targeting TGM1 and a scrambled negative control were obtained from Invitrogen (Carlsbad, CA). The293T and HaCaT cells were transfected with over-expression clones carry either wild-type or mutated TGM1sequence. Cells were harvested 48 hours post-transfection.
2015-12-31 | E-GEOD-70859 | biostudies-arrayexpress
Project description:Autosomal recessive congenital ichthyoses (ARCI) are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Epidermis-specific conditional knockout of Alox12b encoding 12R-LOX was established in mice using the Cre-Lox system. Tamoxifen-induced Alox12b inactivation in mouse skin caused an ichthyosis-like phenotype. We used microarray to compare the gene expression profile in the epidermis of mice after tamoxifen induced Alox12b inactivation with that of control animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127434 | GEO
Project description:Autosomal recessive congenital ichthyoses are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Mice with targeted inactivation of the 12R-LOX gene Alox12b were established .Heterozygous mutant mice (Alox12b+/−) were bred with 129S6, and their heterozygous offspring were intercrossed to obtain homozygous mutant mice. Homozygous Alox12b knockout mice died within 3 hours after birth owing to defective skin barrier function. We used microarray to compare the gene expression profile in the epidermis of Alox12b-null mice with that of wildtype animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127435 | GEO
Project description:Autosomal recessive congenital ichthyosis (ARCI) is a group of rare inherited skin disorders characterized by remarkable hyperkeratosis. Transglutaminase 1 (TGM1) mutations have been reported to be involved in four different phenotypes of ARCI, including lamellar ichthyosis (LI), non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit ichthyosis (BSI), and self-improving collodion ichthyosis (SICI) according to the clinical presentation and histopathology. TGM1 has been found as a defective gene in a large amount of patients with LI and some patients with NBCIE, BSI and SICI. To further understand the effect of TGM1 mutations in epidermal cells development, we performed the transcriptome analysis of HEK293T and HaCaT cells transfected with TGM1 shRNA, TGM1 wild-type and mutant clones. The transcriptomic analysis revealed the effects of TGM1 on cell-cell interaction by suppressing genes involved in the gap junctions, tight junctions and desmosomes. These findings suggested that the TGM1 deficiency disturbed the balance of keratinocytes proliferation and differentiation processes and impaired the epithelial barrier function. The results provided the basis for further understanding on the etiology of ARCI.
2015-12-31 | GSE70859 | GEO
Project description:Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of monogenic skin disorders caused by mutations in any of >10 different genes, many of which are involved in epidermal synthesis of ω-O-acylceramides (acylCer), an essential precursor of the corneocyte lipid envelope that is also dependent on transglutaminase-1 for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations, the most common cause of ARCI, might lead to a compensatory overexpression of transcripts involved in barrier repair, including ARCI-causing genes. Using microarray we examined the global mRNA expression profile in skin biopsies from five ARCI-patients with TGM1 mutations and four healthy controls. There were a total of 602 differentially expressed genes (adjusted P<0.05). Gene ontology analysis showed enrichment of mRNA encoding proteins associated with biological pathways mainly involved in keratinocyte differentiation and adaptive/innate immune response. Moreover, among non-syndromic ARCI-causing genes, seven out of twelve were significantly increased (log2fold -change=0.98-2.05). Four genes causing syndromic ichthyosis and seven other genes involved in biosynthesis of fatty acyl-CoA and ceramides were also significantly affected. This study reveals upregulation of several ichthyosis-causing genes in the skin of patients with TGM1 mutations, indicating a compensatory induction of acylCer biosynthesis as a part of a barrier repair mechanism.
2018-11-30 | GSE107462 | GEO
Project description:Mutations in PNPLA1 (patatin-like phospholipase domain containing 1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in highly differentiated keratinocytes, plays a crucial role in the biosynthesis of acylceramide, a lipid component essential for skin barrier function. Pnpla1-deficient mice showed neonatal lethality due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and impaired terminal differentiation of keratinocytes. In Pnpla1–/– epidermis, three unique linoleate-containing lipids, including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids, were almost absent with reciprocal increases in their precursors ω-hydroxy (glucosyl)ceramides and ω-hydroxy fatty acids, indicating that PNPLA1 catalyzes the ω-O-esterification step with linoleic acid to form acylceramides. Our results suggest that PNPLA1 represents the missing piece in the process of acylceramide biosynthesis required for establishment of a permeability barrier.
2016-12-23 | GSE87682 | GEO
Project description:Ichthyosis Curth–Macklin is a rare genetic disorder that is clinically characterized by severe palmoplantar keratoderma. We have described previously a severe familial phenotype caused by a novel mutation in the KRT1 gene. In this study, we analyzed the skin of one patient using gene expression microarrays. We used microarrays to study the differences of gene expression between normal skin and skin affected by Ichthyosis Curth-Macklin
2015-09-29 | GSE73512 | GEO
Project description:Purpose: Determine new therapeutic targets for a refractory drug-induced hypersensitivity syndrome/DRESS using single cell transcriptomic analysis. Methods: Skin cells were dissociated from skin biopsies of a patient with DRESS and 5 healthy volunteers using enzymatic digestion, then viable skin cells were sorted using flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood using Ficoll-paque density separation. PBMCs were cultured with or without medications for 4 days. In detail, 200,000 PBMCs were cultivated in 200ul of RPMI-1640 supplemented with 10% human AB serum with (PBMC_T4_BACT) or without (PBMC_T4_CTRL) 48 ug/mL sulfamethoxazole/trimethoprim (SMX-TMP). For the in vitro therapeutic experiments, PBMCs were cultured in the presence of SMX-TMP with (DRESS_Day4_TOFA) or without (DRESS_Day4_BACT) tofacitinib. The patient was treated with 10mg/d of tofacitinib, a JAK3 inhibitor. The freshly isolated PBMCs were collected again two weeks after initiation of intervention (PBMC_POST2W). Single cells from the skin, freshly isolated PBMCs, and culture PBMCs were captured using droplet based single-cell approach (10x Genomics) and library were prepared. Results: The lymphocytes in skin and PBMCs exhibited upregulation of skin-homing chemokine receptors, CCR4 and CCR10, and JAK3 and STAT1. Treatment with tofacitinib dramatically extinguished skin inflammation in a chronic refractory case of DiHS/DRESS. Conclusions: A successful intervention with tofacitinib in a refractory case of DiHS/DRESS was guided by the use of scRNAseq, which demonstrated aberrant activity in the JAK-STAT pathway.
2019-06-17 | GSE132802 | GEO