Ontogenic Identification and Analysis of Mesenchymal Stromal Cell Populations during Mouse Limb and Long Bone Development.

Ontogenic Identification and Analysis of Mesenchymal Stromal Cell Populations during Mouse Limb and Long Bone Development.
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DOI:
10.1016/j.stemcr.2017.08.007
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发表时间:
2017-10-10
期刊:
影响因子:
5.9
通讯作者:
Zeller R
Zeller R
中科院分区:
医学1区
文献类型:
--
作者:
Nusspaumer G;Jaiswal S;Barbero A;Reinhardt R;Ishay Ronen D;Haumer A;Lufkin T;Martin I;Zeller R

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骨源性间充质基质细胞(MSCs)分化成多个谱系,包括软骨和成骨命运和功能,建立骨髓造血区室。在这里,我们分析了小鼠四肢和长骨发育过程中不同MSC类型的出现。特别是,在PDGFR α posCD 51 pos(Pα CD 51)间充质祖细胞中检测到PDGFR αposSCA-1 pos(PαS)细胞和小鼠骨骼干细胞(mSSC),这是早期肢芽和出生前发育中长骨中最丰富的祖细胞。长骨来源的PαS细胞和mSSC在新生小鼠中最常见,分子分析表明,它们从最早期开始就构成了不同的祖细胞群。CD 90和CD 73的差异表达鉴定了4个PαS亚群,它们显示出不同的软骨和成骨分化潜能。最后,我们表明,从CD 90 pos PαS细胞产生的软骨结构被重塑成包含功能性内皮和造血区室的骨类器官,这使得这些细胞适合用于骨组织工程。小鼠四肢和长骨发育过程中MSC群体的个体发生谱Pα CD 51阳性细胞是最普遍的间充质群体PαS细胞和mSSC作为Pα CD 51祖细胞库中的不同群体出现。来自一个PαS亚群的Carbohydrate构建体被重塑为骨类器官在这篇文章中,Zeller和他的同事表明,在小鼠胚胎肢体和长骨发育的特定时间点,功能不同的MSC群体出现,并在体内平衡期间持续存在。特别是,PαS亚群具有形成结构良好的骨类器官的能力,包括功能性内皮和造血隔室,这与骨组织工程有关。
Bone-derived mesenchymal stromal cells (MSCs) differentiate into multiple lineages including chondro- and osteogenic fates and function in establishing the hematopoietic compartment of the bone marrow. Here, we analyze the emergence of different MSC types during mouse limb and long bone development. In particular, PDGFRαposSCA-1pos (PαS) cells and mouse skeletal stem cells (mSSCs) are detected within the PDGFRαposCD51pos (PαCD51) mesenchymal progenitors, which are the most abundant progenitors in early limb buds and developing long bones until birth. Long-bone-derived PαS cells and mSSCs are most prevalent in newborn mice, and molecular analysis shows that they constitute distinct progenitor populations from the earliest stages onward. Differential expression of CD90 and CD73 identifies four PαS subpopulations that display distinct chondro- and osteogenic differentiation potentials. Finally, we show that cartilage constructs generated from CD90pos PαS cells are remodeled into bone organoids encompassing functional endothelial and hematopoietic compartments, which makes these cells suited for bone tissue engineering. Ontogenic profiling of MSC populations during mouse limb and long bone development PαCD51-positive cells are the most prevalent mesenchymal population PαS cells and mSSCs arise as distinct populations within the PαCD51 progenitor pool Cartilage constructs from one PαS subpopulation are remodeled into bone organoids In this article, Zeller and colleagues show that functionally distinct MSC populations arise at specific time points during mouse embryonic limb and long bone development and persist during homeostasis. In particular, a PαS subpopulation with the ability to form well-structured bone organoids encompassing functional endothelial and hematopoietic compartments is identified, which is of relevance for bone tissue engineering.
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