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RNA-Seq analysis of Harlequin Ichrthyosis skin, HI 3D model ABCA12 CRISPR-Cas9 KO cell line

ABSTRACT: RNA-Seq analysis of Harlequin Ichrthyosis skin, HI 3D model ABCA12 CRISPR-Cas9 KO cell line

PROVIDER: PRJNA545285 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12080100_1.fastq.gz	Fastqsanger.gz
	SRR12080100_2.fastq.gz	Fastqsanger.gz
	SRR12080077_1.fastq.gz	Fastqsanger.gz
	SRR12080077_2.fastq.gz	Fastqsanger.gz
	SRR12080078_1.fastq.gz	Fastqsanger.gz

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RNA-Seq analysis of Harlequin Ichrthyosis skin, HI 3D model ABCA12 CRISPR-Cas9 KO cell line

Project description:The biology of Harlequin Ichthyosis (HI), a devastating skin disorder, caused by loss of function mutations in the gene ABCA12, is poorly understood and to date no satisfactory treatment has been developed. We sought to investigate pathomechanisms of Harlequin Ichthyosis which could lead to the identification of safe and effective treatments to improve patients' quality of life. RNA-Seq analysis using normal skin (n=5) and HI patient skin (n=4) were performed to define the effects of loss of ABCA12. Functional annotation clustering analysis showed changes in three common groups: epidermal differentiation, lipid metabolism and inflammation (innate immunity and IFNγ signalling). In HI patient skin, gene expression of STAT1, STAT3 and Interleukin 36 (IL-36) A and G cytokines was significantly upregulated compared to normal skin, whereas IL-37, an inhibitor of innate immunity, was downregulated. RNA-Seq and functional assays were performed to define the effects of loss of ABCA12, using an engineered CRISPR-Cas9 ABCA12 KO 3D model. Functional annotation clustering analysis showed changes in three common groups: epidermal differentiation, lipid metabolism and inflammation.

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