Winchester, E. W. | bioRxiv Science

bioRxiv2022

Integrative analysis of transcriptomics in human craniofacial development reveals novel candidate disease genes

Craniofacial disorders are among the most common of all congenital defects. A majority of craniofacial development occurs early in pregnancy and to fully understand how craniofacial defects arise, it is essential to observe gene expression during this critical time period. To address this we performed bulk and single-cell RNA-seq on human craniofacial tissue from embryonic development 4 to 8 weeks post conception. This data comprises the most comprehensive profiling of the transcriptome in the early developing human face to date. We identified 239 genes that were specifically expressed in craniofacial tissues relative to dozens of other human tissues and stages. We found that craniofacial specific enhancers are enriched within 400kb of these genes establishing putative regulatory interactions. To further understand how genes are organized in this program we constructed coexpression networks. Strong disease candidates are likely genes that are coexpressed with many other genes, serving as regulatory hubs within these networks. We leveraged large functional genomics databases including GTEx and GnomAD to reveal hub genes that are specifically expressed in craniofacial tissue and genes which are resistant to mutation in the normal healthy population. Our unbiased method revealed dozens of novel disease candidate genes that warrant further study.

genomics↗

bioRxiv2021

Identification of enamel knot gene signature within the developing mouse molar

In most mammals, the primary teeth develop in utero and the cells capable of contributing to hard surface regeneration are lost before tooth eruption. These cells differentiate through a series of reciprocal induction steps between the epithelium and mesenchyme, initially orchestrated by an epithelial signaling center called the enamel knot. While the factors secreted by this structure are of interest to the dental regeneration and development communities, its small size makes it difficult to isolate for analysis. Here we describe our work to identify the enamel knot from whole E14 molars using publicly available scRNA-seq data. We identified 335 genes differentially expressed in the enamel knot compared to the surrounding tissues, including known enamel knot marker genes. We validated expression of the most highly enriched enamel knot marker genes and identified 42 novel marker genes of the enamel knot which provide excellent targets for future dental regeneration investigations.

developmental biology↗