Modulated expression of NOTCH1 during thymocyte development
Modulated expression of NOTCH1 during thymocyte development
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DOI：
10.1182/blood.v88.3.970.bloodjournal883970
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发表时间：
1996-08-01
期刊：
影响因子：
20.3
通讯作者：
Sklar, J
中科院分区：
文献类型：
--
作者：
Hasserjian, RP;Aster, JC;Sklar, J
Notch基因家族编码的跨膜蛋白参与了果蝇、青蛙和小鼠中多种细胞分化事件的控制。哺乳动物Notch 1在胸腺中高水平表达，并在人T细胞急性淋巴细胞肿瘤的一个亚群中突变，表明其在if细胞分化中的作用。为了研究Notch 1蛋白在发育和成熟胸腺的胸腺细胞中的表达模式，使用针对NOTCH 1产生的抗体进行免疫组织化学和流式细胞术分析。早在胚胎移植后13.5天就观察到胎鼠胸腺内的NOTCH 1强染色。到17.5天后，观察到表层皮质胸腺细胞的优先染色，发育中的髓质染色较弱。流式细胞术分析和流式分选细胞的免疫组化染色证实，成年小鼠胸腺中最高水平的NOTCH 1表达存在于未成熟的皮质胸腺细胞中（CD 24高，CD 4（-）CD 8（-））。相比之下，在更成熟的皮质胸腺细胞（CD 24低，CD 4（+）CD 8（+））中，NOTCH 1表达较低或不表达，而在CD 4（+）CD 8（-）和CD 4（-）CD 8（+）细胞中观察到中等水平的表达。这些数据表明在T细胞分化过程中NOTCH 1表达的动态模式，并表明NOTCH 1的下调可能是皮质胸腺细胞成熟所必需的。(C)1996年，美国血液学会。
The Notch gene family encodes transmembrane proteins that have been implicated in control of diverse cellular differentiation events in the fly, frog, and mouse, Mammalian Notch1 is expressed at high levels in thymus and is mutated in a subset of human T-cell acute lymphoblastic neoplasms, suggesting a role in if-cell differentiation, To investigate the patterns of expression of NOTCH1 protein in thymocytes of the developing and mature thymus, antibodies raised against NOTCH1 were used to perform immunohistochemical and flow cytometric analyses. Strong staining for NOTCH1 within the fetal murine thymus was observed as early as 13.5 days postcoitum. By 17.5 days postcoitum preferential staining of superficial cortical thymocytes was observed, with weak staining of developing medulla. Flow cytometric analysis and immunohistochemical staining of flow-sorted cells confirmed that the highest levels of NOTCH1 expression in adult murine thymus were present in immature cortical thymocytes (CD24high, CD4(-)CD8(-)). In contrast, NOTCH1 expression was low or absent in more mature cortical thymocytes (CD24low, CD4(+)CD8(+)), whereas intermediate levels of expression were observed in CD4(+)CD8(-) and CD4(-)CD8(+) cells. These data indicate a dynamic pattern of NOTCH1 expression during T-cell differentiation and suggest that downregulation of NOTCH1 may be required for maturation of cortical thymocytes. (C) 1996 by The American Society of Hematology.