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Dynamic enhancer landscapes in human craniofacial development [scRNA-seq]

ABSTRACT: Dynamic enhancer landscapes in human craniofacial development [scRNA-seq]

PROVIDER: PRJNA987563 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25032800_1.fastq.gz	Fastqsanger.gz
	SRR25032800_2.fastq.gz	Fastqsanger.gz
	SRR25032801_1.fastq.gz	Fastqsanger.gz
	SRR25032801_2.fastq.gz	Fastqsanger.gz
	SRR25032802_1.fastq.gz	Fastqsanger.gz

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Project description:The genetic basis of craniofacial birth defects and general variation in human facial shape remains poorly understood. Distant-acting transcriptional enhancers are a major category of non-coding genome function and have been shown to control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic location and cell type-specific in vivo activities of all craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combined transcriptome, histone modification, and chromatin accessibility profiling from different stages of human craniofacial development with single-cell analyses of the developing mouse face to create a comprehensive catalogue of the regulatory landscape of facial development at tissue- and single cell-resolution. In total, we identified approximately 14,000 enhancers across seven developmental stages from weeks 4 through 8 of human embryonic face development. To annotate the cell type specificity of human-mouse conserved enhancers, we performed single-cell RNA-seq and single-nucleus ATAC-seq of mouse craniofacial tissues from embryonic days e11.5 to e15.5. By integrating across these data sets, we identify major cell populations of the developing face and annotate over 16,000 candidate enhancers by their cell type-specific epigenomic profile. Using retrospective analysis of known craniofacial enhancers in combination with single cell-resolved transgenic reporter assays, we show the value of these data for the prediction of in vivo cell type specificity. Taken together, our data provide a critical resource for genetic and developmental studies of human craniofacial development.

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