Dynamic enhancer landscapes in human craniofacial development

作者：Sudha Rajderkar, Kitt Paraiso, Maria Luisa Amaral, Michael Kosicki, Laura Cook, Fabrice Darbellay, Cailyn H. Spurrell, Marco Osterwalder, Yiwen Zhu, Han Wu, Sarah Afzal, Matthew J. Blow, Guy Kelman, Iros Barozzi, Yoko Fukuda-Yuzawa, Jennifer A. Akiyama, Veena Afzal, Stella Tran, Ingrid Plajzer-Frick, Catherine S. Novak, Momoe Kato, Riana D. Hunter, Kianna von Maydell, Allen Wang, Lin Lin, Sebastian Preißl, Steven Lisgo, Bing Ren, Diane E. Dickel, L Pennacchio, Axel Visel · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-46396-4 · 被引用次数：29 · 研究领域：Single-cell and spatial transcriptomics、Epigenetics and DNA Methylation、Genomics and Chromatin Dynamics

The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.