A NOTCH2 Pathogenic Variant Alters the Osteoblast and Vascular Cell Transcriptome of Mouse Femurs

A recently reported novel NOTCH2 4006G>C variant was associated with decreased Notch signaling and skeletal fragility in humans and mouse (Notch2em1Ecan) lines. In the present study, we analyze the transcriptome of femoral bones from mature control and Notch2em1Ecan mice following the exclusion of hematological cells.

Single cells were analyzed following microfluidic partitioning on a Chromium X instrument using a 3' gene expression library. Uniform manifold approximation and projection (UMAP) for non-linear dimensional reduction defined 15 different cell clusters comprised of macrophages, red blood cells, endothelial, vascular and smooth and striated muscle cells and cells of the osteoblast lineage. Notch2 and Hes1 were the prevalent Notch receptor and target gene in most clusters.