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MRNA changes during primary human keratinocyte differentiation

ABSTRACT: mRNA changes during primary human keratinocyte differentiation

PROVIDER: PRJNA950894 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24033160_1.fastq.gz	Fastqsanger.gz
	SRR24033160_2.fastq.gz	Fastqsanger.gz
	SRR24033161_1.fastq.gz	Fastqsanger.gz
	SRR24033161_2.fastq.gz	Fastqsanger.gz
	SRR24033162_1.fastq.gz	Fastqsanger.gz

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Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses

Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell transcriptomics, methylomics and multi-omics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the subclasses with an epigenetic mitotic-like clock, and the study of other unstratified KC entities uncovered distinct phenotypic and clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis

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