|
Fig. 3 Spatiotemporal expression pattern of known HSCR genes and newly identified HSCR-associated genes in the developing intestine of human and mice foetuses. (a) Spatial expression of the HSCR-associated genes. The three cell types (neural crest cells, enteric neurons, and FRZB fibroblast cells) in human developing intestine enriched with HSCR-associated genes are highlighted in bold on the y-axis. Known and novel HSCR-associated genes identified from the current meta-analysis are highlighted in bold and red respectively on the x-axis. Differentially expressed genes (log2 fold change>1 and adjusted p-value <0.01, Wilcoxon rank-sum test) are marked by ∗ (p < 0.01) and ∗∗ (p < 0.001) in the corresponding cell type. Epi, epithelial cells; SMC, smooth muscle cells; FLC, fibroblast cells; ICC, interstitial cells of Cajal; EC, endothelial cells; (b) Temporal expression of the HSCR-associated genes. Candidate risk genes demonstrated signals of overexpression primarily at two developmental (F6.1 and F8.4) time points. (c) Expression patterns for the HSCR-associated genes in the developing ENS of mice using single cell transcriptome integrated from data at E13.5, E15.5 and E18.5. Zfp9 represents the mouse orthologue to human ZNF25. Jag1 is mainly expressed in the mesenchyme and thus the expression pattern of its receptor, Notch1, is shown. Branch A and B neurons were defined analogously to human Gut Cell Altas based on the cell-type specific markers of Etv1 and Bnc2 respectively. UMAP plots stratified by three developmental time points are included in Supplementary Figure S22.