Single-cell RNA sequencing unravels heterogeneity of skeletal progenitors underlying the bone repair process

To better understand the behavior of the skeletal progenitors and the heterogeneity of the cells during bone repair process at the microenvironmental level, a combinational analysis consisting of lineage tracing for skeletal progenitors using the Sox9-CreERT2;R26RtdTomato mouse line followed by single-cell RNA sequencing (scRNA-seq) analysis using a mouse model of calvarial bone repair was performed. We further performed computational analysis focusing on the identification of the cell-cell interactions, followed by pharmacological assessments with a critical-size calvarial bone defect mouse model. We characterized multipotential skeletal progenitors and identified a key signaling pathway to direct the osteoblast differentiation in the model.