Inactivation of Hes1 in skeletal undifferentiated cells increases bone volume

Neither osteogenesis nor adipogenesis were modified by the Hes1 deletion in bone marrow stromal cell cultures, although Tnfsf11 (encoding RANKL) was suppressed in osteogenic cultures of Hes1∆/∆ cells. Single cell RNA sequencing of femurs from 5-month-old LepR-Cre;Hes1∆/∆ and control mice revealed the presence of 23 cell clusters including clusters composed of hematological cells (myeloid, B cells and neutrophils), endothelial cells and osteoblasts.

There were no substantial differences in gene expression, cluster distribution or trajectory finding between control and Hes1 inactivated cells. In conclusion, Hes1 inactivation in LepR+ cells results in an increase in bone mass secondary to a decrease in RANKL, osteoclast number and bone resorption, but HES1 has little influence on osteogenesis or adipogenesis in bone.