Skeletal Site-Specific Variations in CD11b+ Cells: Insights from Single Cell RNA Sequencing of the Mandible and Femur [scRNA-Seq]

Osteoclasts of the craniofacial region facilitate processes such as tooth eruption and jawbone development. Evidence suggests that craniofacial osteoclasts exhibit distinct characteristics compared to their counterparts within the appendicular skeleton. A biological mechanism to explain the observable difference between craniofacial osteoclasts and osteoclasts in the long bones has not been previously explored. To further understand differences that exist between the two populations, here we perform an unbiased genetic survey via single-cell RNA sequencing of CD11b+ cells from mandibular- and the femur-derived bone marrow of 2-month-old C57BL/6 mice to further understand differences that exist between the two populations in an unbiased genetic survey. Our results reveal transcriptomic evidence that suggests a uniquely inflammatory genetic profile of the mandibular-derived CD11b+ cells. This correlates with an increase in select areas of open chromatin by ATAC-Sequencing and inflammatory gene expression by RT-qPCR. Further exploration into a specific upregulated genes determined KLF4 was both necessary and important for proper differentiation in mandibular derived cells. Suppression of KLF4 likewise limited gene expression of metabolic transporter MCT2. Because this transporter is well understood to impact lactate transportation into cells, we determined that concentration of intracellular lactate was increased in mandibular derived osteoclasts. Together these data suggest a potential metabolic mechanism for the observable differences seen between craniofacial and appendicular osteoclasts.