C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors.

Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) cohabit in the bone marrow. KITL (C-KIT ligand) from LEPR adult bone marrow stromal cells is pivotal for HSC maintenance. In contrast, it remains unclear whether KITL/C-KIT signaling also regulates SSCs. Here, we lineage traced C-KIT cells and found that C-KIT was expressed by fetal, but not postnatal skeletal progenitors. Fetal C-KIT cells gave rise to 20% of LEPR stromal cells in adult bone marrow, forming nearly half of all osteoblasts. Disruption of mTOR signaling in fetal C-KIT cells impaired bone formation. Notably, conditional deletion of Kitl from PRX1 fetal bone marrow stromal cells, but not LEPR adult bone marrow stromal cells, significantly increased bone formation. Thus, our work identified C-KIT skeletal progenitors as an important source of bones formed during development.