A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.

A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.
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DOI:
10.1038/ncb3067
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发表时间:
2014-12
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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--
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软骨内骨发育的标志是软骨模板的存在,其中生成成骨细胞和基质细胞以形成矿化基质并支持骨髓造血。然而,这些间充质细胞的最终来源以及胎儿期骨祖细胞与晚年骨祖细胞之间的关系尚不清楚。命运图谱研究表明,表达由胶原蛋白 II (Col2) 启动子/增强子驱动的 cre 重组酶的细胞及其后代,除了软骨细胞外,还促成 Runx2 表达之前的早期软骨膜前体,随后形成大多数成骨细胞、Cxcl12(趋化因子(C-X-C 基序)配体 12)丰富的基质细胞和骨髓出生后生活中的基质/间充质祖细胞。使用他莫昔芬诱导的creER系统进行谱系追踪实验进一步表明,由Col2-creER以及Sox9-creER和聚集蛋白聚糖(Acan)-creER标记的早期出生后细胞逐渐形成多种间充质谱系,并持续提供后代一年多。这些细胞与成体间充质祖细胞不同,因此为调节在生长的哺乳动物中独特发生的爆炸性生长提供了机会。
The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow hematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors prior to Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals.
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