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. •C-KIT was expressed by fetal, but not postnatal skeletal progenitors•Fetal C-KIT+ cells formed half of all osteoblasts in adult bone marrow.•Disruption of mTOR signaling in fetal C-KIT+ cells impaired bone formation•Conditional deletion of Kitl from Prx1+ cells significantly increased bone formation In this article, Zhou and colleagues identified fetal C-KIT+ stromal cells as an important source of bones formed during development. These cells gave rise to 20% of LEPR+ stromal cells in adult bone marrow, forming nearly half of all osteoblasts. This work highlights the heterogeneity of skeletal progenitors during development.