Human-mouse cross-species comparison identifies common and unique aspects of intestinal mesenchyme development

Using single-cell RNA sequencing (scRNA-seq) and histological approaches, we examine cross-species cellular identity, diversity and organization of mesenchymal (fibroblast) populations in the developing mouse and human intestines. In both species, we defined 7 fibroblast populations. Using cross-species integration and label transfer approaches we find that each mesenchymal cell subtype in the murine intestine is highly concordant to a cell type/state in the human intestine, and vice-versa, suggesting a strong conservation of mesenchymal cell types/states across species. Despite this conservation, we also observe that individual lineage-defining genes are not always shared and can be found in different mesenchymal populations. High resolution spatial analysis via fluorescent in situ hybridization (FISH) and immunofluorescence (IF) confirmed these findings and revealed that transcriptionally-defined sub-types of intestinal mesenchymal cells in mice and humans are organized within similar spatial domains.