C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors
Autor: | Guangdun Peng, Yujie Chen, Naihe Jing, Wenjie Dong, Xiujuan Yin, Xinyu Thomas Tang, Bo O. Zhou, Di Demi He, Guizhong Cui |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Stromal cell Bone Marrow Cells Biology bone Biochemistry Article Bone and Bones skeletal progenitors Mice 03 medical and health sciences Chondrocytes Fetus 0302 clinical medicine Osteogenesis Adipocytes Genetics medicine Animals Cell Lineage Bone formation Progenitor cell Stem Cell Factor Bone Development Osteoblasts Stem Cells SCF Mesenchymal Stem Cells KITL Cell Biology hematopoietic stem cells Cell biology C-KIT Proto-Oncogene Proteins c-kit Haematopoiesis 030104 developmental biology medicine.anatomical_structure skeletal stem cells Animals Newborn Bone marrow Stem cell Transcriptome Gene Deletion 030217 neurology & neurosurgery Increased bone formation Signal Transduction Developmental Biology |
Zdroj: | Stem Cell Reports |
ISSN: | 2213-6711 |
DOI: | 10.1016/j.stemcr.2020.03.001 |
Popis: | Summary 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. Highlights • 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. |
Databáze: | OpenAIRE |
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