Dynamics of thymus organogenesis and colonization in early human development.

Dynamics of thymus organogenesis and colonization in early human development.
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DOI:
10.1242/dev.087320
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发表时间:
2013-05
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Blackburn CC
Blackburn CC
中科院分区:
其他
文献类型:
--
作者:
Farley AM;Morris LX;Vroegindeweij E;Depreter ML;Vaidya H;Stenhouse FH;Tomlinson SR;Anderson RA;Cupedo T;Cornelissen JJ;Blackburn CC

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胸腺是T细胞发育的中心部位,因此对免疫系统至关重要,但关于人类胸腺发育的分子调控的信息很少。在这里,我们证明,通过空间和时间的表达分析,已知的调节小鼠胸腺器官发生的遗传机制是保守的人类。此外,我们提供了分子证据,证明人类胸腺上皮仅源自第三咽囊,就像小鼠一样,这与之前的建议相反。最后,我们定义了造血细胞定植和上皮细胞分化在人胸腺原基的发病时间,出乎意料地显示,第一个定植的造血细胞是CD 45 + CD 34 int/-。总的来说,我们的数据为将小鼠中建立的原则转化为人类提供了必要的信息,并且与开发用于增强患者免疫重建的改进策略特别相关。
The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45+CD34int/-. Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients.
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