Cell types, positional codes, and enhancers contributing to human facial individuality and pathology

Le résumé fourni par la source

We created a multi-modal facial atlas across embryonic weeks 6-11, providing single cell transcriptomics, chromatin accessibility and spatial transcriptomics, all at single cell resolution. We characterized 56 cell states, mapping mesenchymal subtypes and their gene-enhancer cis-regulatory landscapes in space and time. Gene expression associations with facial traits were strongest in early mesenchymal progenitor cells, gradually becoming more region-restricted. Autocorrelation analysis revealed patterning genes that define spatial neighborhoods of mesenchyme, potentially explaining trait-specificity of their nearby variants. Enhancers of key disease-related genes were found to be likely vehicles for generating facial variation in modern human populations. One such enhancer, linked to PAX1 expression, appears to be essential for normal skeletal development in mice. Finally, GWAS prediction, cell signaling interaction analysis and validation in mice revealed that peripheral nerves fine-tune maxilla shape during embryonic development. This multi-modal atlas should be a useful resource for researchers studying mechanisms of craniofacial disorders and the gene regulatory mechanisms driving human facial individuality.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.