Early T-cell progenitors are the major granulocyte precursors in the adult mouse thymus
Early T-cell progenitors are the major granulocyte precursors in the adult mouse thymus
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DOI：
10.1182/blood-2012-08-451773
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发表时间：
2013-01-03
期刊：
影响因子：
20.3
通讯作者：
Bhandoola, Avinash
中科院分区：
文献类型：
--
作者：
De Obaldia, Maria Elena;Bell, J. Jeremiah;Bhandoola, Avinash
小鼠胸腺支持T细胞发育，但也包含非T细胞谱系，如树突状细胞、巨噬细胞和粒细胞，这是选择T细胞谱系和清除胸腺细胞凋亡所必需的。体外和体内实验表明，早期胸腺祖细胞(ETP)并不依赖于T细胞谱系。ETPs是否在体内实现了非T细胞的谱系潜能，目前还不清楚，而且确实存在争议。在目前的研究中，我们调查了ETP是否是胸腺中任何非T细胞的主要前体。我们分析了这些群体在实验环境下的发育情况，在实验环境中，由于胸腺沉积被取消或IL-7受体α或Hes1的遗传消融抑制了早期胸腺发育，ETP几乎不存在。用多种体内方法获得的结果表明，胸腺粒细胞的大部分来源于ETPs。这些数据表明，骨髓淋巴前体细胞稳定胸腺，从而阐明干细胞产生下游血细胞谱系的途径。(血。2013年；第121(1)：-71)
The mouse thymus supports T-cell development, but also contains non-T-cell lineages such as dendritic cells, macrophages, and granulocytes that are necessary for T-cell repertoire selection and apoptotic thymocyte clearance. Early thymic progenitors (ETPs) are not committed to the T-cell lineage, as demonstrated by both in vitro and in vivo assays. Whether ETPs realize non-T-cell lineage potentials in vivo is not well understood and indeed is controversial. In the present study, we investigated whether ETPs are the major precursors of any non-T-lineage cells in the thymus. We analyzed the development of these populations under experimental circumstances in which ETPs are nearly absent due to either abrogated thymic settling or inhibition of early thymic development by genetic ablation of IL-7 receptor alpha or Hes1. Results obtained using multiple in vivo approaches indicate that the majority of thymic granulocytes derive from ETPs. These data indicate that myelolymphoid progenitors settle the thymus and thus clarify the pathways by which stem cells give rise to downstream blood cell lineages. (Blood. 2013;121(1): 64-71)