Identification of adipo-osteoprogenitors in murine bone marrow
The bone marrow in mammals house both hematopoietic and mesenchymal cells that are responsible for sustaining blood and bone cell production, respectively, throughout adult life. Although the hematopoietic system is well understood, the molecular identities, hierarchy of the marrow mesenchymal cells and their respective contribution to bone homeostasis are just beginning to be unraveled. By employing single-cell RNA sequencing (scRNA-seq) technology, we have discovered a subset of bone marrow mesenchymal cells co-expressing adiponectin (Adipoq) and osterix (Osx) which are traditionally considered adipocyte or osteoblast markers, respectively. Trajectory analyses predict the Adipoq+Osx+ bi-marker cells to be common progenitors for osteoblasts and marrow adipogenic lineage cells. Lineage tracing with Osx-CreERT2 or Adipoq-CreERT2 supports that the bi-marker cells give rise to both osteoblasts and adipocytes in vivo. Imaging studies localize the bi-marker cells to the endosteal bone niche. The data therefore support the hypothesis that Adipoq+Osx+ bi-marker cells are adipo-osteoprogenitors attuned to the physiological milieu in the bone marrow. The studies have shed light on the role of the adipo- osteoprogenitors in bone physiology and pathophysiology. Overall design: Identification and illuminating of adipo-osteoprogenitors (Osteo-CAR) in murine bone marrow