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Institute of Biochemistry and Cell Biology, Chinese Academy of Scienceshttps://www.ebi.ac.uk/ena/browser/view/PRJNA608960Mus musculusxref:EuropePMC:PMC7650646xref:PubMed:32220331c-kit signaling plays pivotal roles in regulating the self-renewal and/or differentiation of many adult stem cells, such as hematopoietic stem cells. However, it remains controversial whether c-kit is expressed by and contribute to skeletal stem cells (SSCs). To test this, we lineage-traced c-kit+ cells and investigated the physiological importance of c-kit+ cells and c-kit signaling in bone development. We found that c-kit was not expressed by postnatal SSCs, but by fetal SSC precursors at the growth cartilage. Lineage-tracing of fetal c-kit+ cells marked approximately 20% of Lepr+ bone marrow stromal cells, generating nearly half of all osteoblasts in adult bone marrow. Disruption of mTOR signaling in c-kit+ cells impaired bone formation. Conditional deletion of Kitl (c-kit ligand, also known as Scf) from fetal, but not adult bone marrow stromal cells increased bone formation. Together, our work identified c-kit+ SSC precursors as an important source of bones formed during development. The osteogenic differentiation of these cells is temporally inhibited by Kitl from the bone marrow microenvironment. Overall design: We performed single-cell RNA sequencing (scRNA-seq) of CD45-Ter119-CD31-PDGFRα+ bone marrow stromal cells from 2-month-old KitMerCreMer R26tdTomato mice that had been treated with tamoxifen at E12.5/14.5ENAColony Forming Unit, Progenitor Cells, Colony-Forming Units, Progenitor Cell, Tr-kit, Xkl-1, Cell, PBT, Gsfsco1, Colony-Forming Unit, scfr, Stem Cell, medulla ossium, Marrow, medulla ossea, SCO5, Mother Cells, kl1-A, SCO1, Yellow, Gsfsow3, SCFR, Gsfsco5, Progenitor, SOW3, XKrk1, Mother Cell, pbt, Yellow Marrow, Fdc, c-KIT, medullary bone, medulla of bone, Stem, Mother, stem cell, Bone Growth, Colony Forming Units, W, kit, CD117, animal stem cell, c-kit, signalling process, C-Kit, Ssm, Cells, xkl-1, Red, Bs, Bone, single organism signaling, Red Marrow., krk1Colony Forming Unit, Progenitor Cells, Colony-Forming Units, Progenitor Cell, Tr-kit, Xkl-1, Cell, PBT, Gsfsco1, Colony-Forming Unit, scfr, Stem Cell, medulla ossium, Marrow, medulla ossea, SCO5, Mother Cells, kl1-A, SCO1, Yellow, Gsfsow3, SCFR, Gsfsco5, Progenitor, SOW3, XKrk1, Mother Cell, pbt, Yellow Marrow, Fdc, c-KIT, medullary bone, medulla of bone, Stem, Mother, stem cell, Bone Growth, Colony Forming Units, W, kit, CD117, animal stem cell, c-kit, signalling process, C-Kit, Ssm, Cells, xkl-1, Red, Bs, Bone, single organism signaling, Red Marrow., krk1falsec-kit Signaling Inhibits Bone Development by Regulating Skeletal Stem Cell Precursors in Fetal Bone Marrowc-kit Signaling Inhibits Bone Development by Regulating Skeletal Stem Cell Precursors in Fetal Bone Marrow2025-09-242020-03-24PRJNA608960GSE1460021009032220331