C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors
C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors
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C-KIT 表达区分胎儿和产后骨骼祖细胞
DOI：
10.1016/j.stemcr.2020.03.001
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发表时间：
2020-04-14
影响因子：
5.9
通讯作者：
Zhou, Bo O.
中科院分区：
文献类型：
--
作者：
He, Di Demi;Tang, Xinyu Thomas;Zhou, Bo O.
造血干细胞（hsc）和骨骼干细胞（ssc）在骨髓中共存。来自LEPR+成人骨髓基质细胞的KITL （C-KIT配体）对HSC的维持至关重要。相比之下，目前尚不清楚KITL/C-KIT信号是否也调节ssc。在这里，我们追踪了C-KIT+细胞的谱系，发现C-KIT在胎儿而不是出生后的骨骼祖细胞中表达。成人骨髓中，胎儿C-KIT+细胞占LEPR+基质细胞的20%，占所有成骨细胞的近一半。胎儿C-KIT+细胞中mTOR信号的破坏会破坏骨形成。值得注意的是，PRX1（+）胎儿骨髓基质细胞条件缺失Kitl，而LEPR+成人骨髓基质细胞不条件缺失Kitl，显著增加骨形成。因此，我们的工作确定了C-KIT+骨骼祖细胞是发育过程中形成骨骼的重要来源。
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.