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C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors
Di Demi He1, Xinyu Thomas Tang1, Wenjie Dong1
1State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P. R. China.
Stem Cell Reports
|March 30, 2020
Summary
Fetal C-KIT+ skeletal progenitors contribute to bone formation by differentiating into stromal cells and osteoblasts. Disrupting their signaling impacts bone development, highlighting their crucial role.
Area of Science:
- Skeletal biology
- Stem cell research
- Bone development
Background:
- Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) reside in bone marrow.
- KIT ligand (KITL) from LEPR+ adult bone marrow stromal cells maintains HSCs, but its role in SSCs is unknown.
Purpose of the Study:
- To investigate the role of KITL/C-KIT signaling in skeletal stem cells.
- To identify the origin of bone-forming cells during development.
Main Methods:
- Lineage tracing of C-KIT+ cells.
- Genetic manipulation of mTOR signaling and Kitl expression.
- Analysis of bone formation and stromal cell populations.
Main Results:
- C-KIT+ cells were identified as fetal skeletal progenitors, not present in postnatal bone marrow.
- These fetal progenitors differentiated into LEPR+ stromal cells and osteoblasts in adult bone marrow.
- Disrupting mTOR signaling in fetal C-KIT+ cells impaired bone formation.
- Conditional deletion of Kitl in fetal PRX1+ stromal cells, but not adult LEPR+ cells, increased bone formation.
Conclusions:
- Fetal C-KIT+ skeletal progenitors are a significant source of osteoblasts during development.
- KITL/C-KIT signaling in these progenitors is critical for regulating bone formation.
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