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- W4366171917 abstract "Zinc finger protein 750 (ZNF50) encodes an epithelial transcription factor with key roles duringin-vitro keratinocyte differentiation, and its autosomal dominant mutation causes a psoriasis-like skin disease. Moreover, alterations in ZNF750 are associated with epithelial cancers, together with cellular studies suggesting a tumor suppressor function for ZNF750. However, the precise in-vivo roles of ZNF750 in tissue development and homeostasis are yet to be elucidated. Here, we report the generation of a Znf750 conditional knockout (cKO) mouse model. Deletion of Znf750 in developing mouse skin using K14-Cre resulted in a delayed barrier acquisition, increased trans-epidermal water loss, and perinatal lethality. Notably, despite the requirement of ZNF750 for in-vitro keratinocyte differentiation, Znf750 cKO mice established apparently normal epidermal differentiation and formed a fully developed stratified epidermis. In depth tissue analysis however, revealed ultrastructural defects in the cornified layers of Znf750 cKO epidermis. RNA-seq analysis demonstrated only mild alterations in the expression of epidermal differentiation genes and structural genes, suggesting that compensatory mechanisms preserve epidermal differentiation in the absence of ZNF750. Finally, in contrast to the epidermal differentiation program, we uncovered in Znf750 cKO epidermis massive changes in immune-related pathways, and a dramatic reduction in epidermal residing immune cells. Taken together, our studies demonstrated that while ZNF750 is not essential for the in-vivo epidermal differentiation process per se, it plays diverse roles in regulating barrier functions by controlling the expression of epidermal structural genes, as well as keratinocyte-derived factors that crosstalk with the immune system. Further studies are expected to uncover molecular mechanisms by which ZNF750 crosstalk with the immune system to preserve barrier functions and tissue homeostasis." @default.
- W4366171917 created "2023-04-19" @default.
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- W4366171917 date "2023-05-01" @default.
- W4366171917 modified "2023-09-28" @default.
- W4366171917 title "767 Znf750 regulates skin barrier functions independently of epidermal differentiation" @default.
- W4366171917 doi "https://doi.org/10.1016/j.jid.2023.03.776" @default.
- W4366171917 hasPublicationYear "2023" @default.
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