The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors

The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors
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DOI:
10.1073/pnas.93.12.5742
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发表时间:
1996-06-11
影响因子:
11.1
通讯作者:
Morahan, G
Morahan, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Blackburn, CC;Augustine, CL;Morahan, G

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裸突变(nu)引起胸腺失郁和无毛,但其作用的分子机制尚未确定。为了解决nu在胸腺发生中的作用,我们研究了裸野生型嵌合小鼠裸体胸腺上皮是否可以全部或部分被野生型细胞拯救。详细的免疫组织化学分析表明,裸源性细胞可以在嵌合胸腺中持续存在,但不能参与皮质或髓质上皮网络,裸源性细胞在髓质中存在少数簇状,表达罕见的成年髓质上皮亚群的标记物,裸小鼠的胸腺上皮雏形强烈表达这些标记物,因此可能定义了未成熟的胸腺上皮前体细胞。这些数据提供了nu基因产物细胞自主作用的第一个证据,并且是成熟胸腺上皮所有主要亚群发育所必需的。我们认为nu可以调节胸腺上皮祖细胞的生长和/或分化,而不是决定。
The nude mutation (nu) causes athymia and hairlessness, but the molecular mechanisms by which it acts have not been determined, To address the role of nu in thymogenesis, we investigated whether all or part of the nude thymic epithelium could be rescued by the presence of wildtype cells in nude wild-type chimeric mice, Detailed immunohistochemical analyses revealed that nude-derived cells could persist in the chimeric thymus but could not contribute to cortical or medullary epithelial networks, Nude-derived cells, present in few clusters in the medulla, expressed markers of a rare subpopulation of adult medullary epithelium, The thymic epithelial rudiment of nude mice strongly expressed these same markers, which may therefore define committed immature thymic epithelial precursor cells, To our knowledge, these data provide the first evidence that the nu gene product acts cell-autonomously and is necessary for the development of all major subpopulations of mature thymic epithelium. We propose that nu acts to regulate growth and/or differentiation, but not determination, of thymic epithelial progenitors.