Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors
Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors
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DOI：
10.1073/pnas.0504750102
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发表时间：
2005-10-11
影响因子：
11.1
通讯作者：
de Crombrugghe, B
中科院分区：
文献类型：
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作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
转录因子Sox9在所有软骨祖细胞中表达，在软骨形成中起关键作用。Sox9也在其他组织中表达，包括中枢神经系统、神经嵴、肠道、胰腺、睾丸和心内膜垫，并且在其中一些组织的细胞增殖和分化中起重要作用。为了确定在小鼠胚胎发生过程中表达Sox9的细胞的命运，我们构建了小鼠模型，将一个内部核糖体进入位点前的Cre重组酶基因插入到Sox9基因的3'非翻译区（Sox9 - Cre基因敲入）。在发育的骨骼中，Sox9在早期成骨细胞标记基因Runx2之前表达。利用Sox9 - Cre；ROSA26报告基因（R26R）小鼠进行的细胞命运图谱分析显示，表达Sox9的肢芽间充质细胞可分化为软骨细胞和成骨细胞。此外，在表达Sox9的细胞中Osterix基因失活的突变体表现出软骨内成骨和膜内成骨缺失，以及与Osterix基因缺失突变体相当的成熟成骨细胞缺失。此外，表达Sox9的肢芽间充质细胞也有助于肌腱和滑膜的形成。通过使用Sox9 - Cre；R26R小鼠，我们还能够系统地追踪从胚胎第8.0天到第17.0天表达Sox9的细胞。我们的结果表明，表达Sox9的细胞有助于脊髓所有细胞类型、肠道和胰腺的上皮以及睾丸的间充质的形成。因此，我们的结果有力地表明，在小鼠胚胎发生过程中，所有骨 - 软骨祖细胞以及多种组织中的祖细胞都来源于表达Sox9的前体细胞。
The transcription factor Sox9 is expressed in all chondroprogenitors and has an essential role in chondrogenesis. Sox9 is also expressed in other tissues, including central nervous system, neural crest, intestine, pancreas, testis, and endocardial cushions, and plays a crucial role in cell proliferation and differentiation in several of these tissues. To determine the cell fate of Sox9-expressing cells during mouse embryogenesis, we generated mice in which a Cre recombinase gene preceded by an internal ribosome entry site was inserted into the 3' untranslated region of the Sox9 gene (Sox9-Cre knock-in). In the developing skeleton, Sox9 was expressed before Runx2, an early osteoblast marker gene. Cell fate mapping by using Sox9-Cre;ROSA26 reporter (R26R) mice revealed that Sox9-expressing limb bud mesenchymal cells gave rise to both chondrocytes and osteoblasts. Furthermore, a mutant in which the Osterix gene was inactivated in Sox9-expressing cells exhibited a lack of endochondral and intramembranous ossification and a lack of mature osteoblasts comparable with Osterix-null mutants. In addition, Sox9-expressing limb bud mesenchymal cells also contributed to tendon and synovium formation. By using Sox9-Cre;R26R mice, we also were able to systematically follow Sox9-expressing cells from embryonic day 8.0 to 17.0. Our results showed that Sox9-expressing cells contributed to the formation of all cell types of the spinal cord, epithelium of the intestine pancreas, and mesenchyme of the testis. Thus, our results strongly suggest that all osteo-chondroprogenitor cells, as well as progenitors in a variety of tissues, are derived from Sox9-expressing precursors during mouse embryogenesis.