Distinct skeletal stem cell types orchestrate long bone skeletogenesis.
Distinct skeletal stem cell types orchestrate long bone skeletogenesis.
复制标题
DOI：
10.7554/elife.66063
复制
发表时间：
2021-07-19
期刊：
影响因子：
7.7
通讯作者：
Chan CK
中科院分区：
文献类型：
--
作者：
Ambrosi TH;Sinha R;Steininger HM;Hoover MY;Murphy MP;Koepke LS;Wang Y;Lu WJ;Morri M;Neff NF;Weissman IL;Longaker MT;Chan CK
骨骼干细胞和祖细胞群体对于骨生理学是至关重要的。这些细胞类型的表征仍然局限于异源批量群体，关于它们是独特的还是与先前表征的细胞类型重叠的信息有限。在这里，我们表明，通过全面的功能和单细胞转录组学分析，出生后的小鼠长骨包含至少两种类型的骨祖细胞与真正的骨骼干细胞（SSC）的特点。早期骨软骨细胞SSC（ocSSC）促进长骨生长和修复，而第二种类型，血管周围SSC（pvSSC），与长骨髓共同出现，并有助于塑造造血干细胞生态位和再生需求。我们确定pvSSC而不是ocSSC是骨髓脂肪组织的来源。最后，我们还提供了对残余SSC异质性以及两个空间上不同的细胞群体之间的潜在串扰的见解。这些研究结果全面解决了以前不受重视的南南合作研究的缺点。
Skeletal stem and progenitor cell populations are crucial for bone physiology. Characterization of these cell types remains restricted to heterogenous bulk populations with limited information on whether they are unique or overlap with previously characterized cell types. Here we show, through comprehensive functional and single-cell transcriptomic analyses, that postnatal long bones of mice contain at least two types of bone progenitors with bona fide skeletal stem cell (SSC) characteristics. An early osteochondral SSC (ocSSC) facilitates long bone growth and repair, while a second type, a perivascular SSC (pvSSC), co-emerges with long bone marrow and contributes to shape the hematopoietic stem cell niche and regenerative demand. We establish that pvSSCs, but not ocSSCs, are the origin of bone marrow adipose tissue. Lastly, we also provide insight into residual SSC heterogeneity as well as potential crosstalk between the two spatially distinct cell populations. These findings comprehensively address previously unappreciated shortcomings of SSC research.