ZNF750 plays an important role in skin inflammation induced by POLY IC treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE248486 | GEO | 2024/08/28
REPOSITORIES: GEO
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Project description:ZNF750 plays an important role in skin inflammation induced by POLY IC treatment
| PRJNA1044110 | ENA
Project description:Loss of ARID1A reduced the inflammatory gene expression of human keratinocytes treated with POLY IC
2023-05-08 | GSE231593 | GEO
Project description:The skin epidermis is a constantly renewing stratified epithelial tissue that provides essential protective barrier functions. The major barrier is at the outermost layers of the epidermis, formed by terminally differentiated keratinocytes reinforced by proteins and lipids of their cornified envelope (CE), and disruptions to this process characterizes common skin disorders. ZNF750 is an epithelial transcription factor essential for in vitro keratinocyte differentiation, whose autosomal dominant mutation in humans causes psoriasis-like skin disease. Here, we report epidermal-specific Znf750 conditional knockout mouse model utilized to uncover the role of Znf750 in epidermal development. We show that deletion of Znf750 in the developing skin does not block epidermal differentiation, suggesting in vivo compensatory feedback mechanisms, yet results in impaired barrier function and perinatal lethality. Molecular dissection uncovered ultrastructural defects in the differentiated layers of the epidermis, accompanied by alterations in the expression of ZNF750-dependent genes encoding for key proteins and lipids involved in CE formation, including gene subsets known to be mutated in skin disease with impaired barrier function.
2023-08-01 | GSE235032 | GEO
Project description:Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demostrated that a dominante mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrehic dermatitis. We defined ZNF750 as a nuclear effector that is atrongly activated in and essiential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differnetiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier Gene expression analysis: To determine the differentaition signature for HaCaT keratinocytes, with ZNF750 gene silencing, total RNA was isolated in biologic triplicates from cells induced to differentiate for twelve days and hybridized to Affymerix Human Gene 1.0 ST arrays.
2012-09-24 | E-GEOD-38039 | biostudies-arrayexpress
Project description:Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demonstrated that a dominant mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrheic dermatitis. We defined ZNF750 as a nuclear effector that is strongly activated in and essential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differentiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier
2012-09-24 | GSE38039 | GEO
Project description:Disrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process. Gene expression analysis: To establish a differentiation signature for primary human keratinocytes, with ZNF750-depleted, and Klf4-depleted, total RNA was isolated in biologic duplicate from cells in different conditions and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-02-15 | E-GEOD-32685 | biostudies-arrayexpress
Project description:Analysis of the specific transcriptional changes on DCs provided by direct pattern recogition receptor (PRR) or IFNAR signaling that are required for DC maturation after poly IC stimulation. Results provide important information about the intricate differentiation process of DC maturation and the importance of type I IFNs for DC immunogenicity. WT/IFNA-/- or WT/PRR-/- mixed-chimera mice were injected with 50 ug Poly-IC i.p. in vivo 4 and 14 hr later, wild type and KO CD11chi CD3- DX5- B220- DCs were FACS sorted based on CD45.2 expression. Total RNA was isolated and expression profile was compared between unstimulated and activated WT and KO DCs.
2013-10-01 | E-GEOD-46478 | biostudies-arrayexpress
Project description:Next generation sequencing (RNA-seq) was used to study the global effects of co-treatment of endothelial cells with poly IC and LL-37. This lead to identification of differentially regulated genes and enriched pathways
2019-04-02 | GSE129152 | GEO
Project description:Goal of the experiment was to examine the effects of different Toll-like receptor agonists on the human astrocyte response, in termsof levels of transcripts encoding cytokines, chemokines and theirreceptors. Stathmin and poly IC are considered as agonist for TLR3, LPSas an agonist for TLR4. The manuscript we are about to submit to Journal of Immunology contains these data, and identifies stathmin, aprotein, as a novel TLR3 agonist. We all know that poly IC is, and bycomparing the transcript responses in astrocytes to either poly IC andstathmin, and observing the similarity in these responses, the experiment adds to the evidence that stathmin indeed activates a verysimilar cellular response as poly IC. The LPS-induced response,mediated by TLR4, is included as a reference, to illustrate thatanother TLR-mediated reaction produces quite something different.
2010-02-11 | E-TABM-851 | biostudies-arrayexpress
Project description:Analysis of the specific transcriptional changes on DCs provided by direct pattern recogition receptor (PRR) or IFNAR signaling that are required for DC maturation after poly IC stimulation. Results provide important information about the intricate differentiation process of DC maturation and the importance of type I IFNs for DC immunogenicity.
2013-10-01 | GSE46478 | GEO