Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes
Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes
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DOI：
10.1073/pnas.95.2.657
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发表时间：
1998-01-20
影响因子：
11.1
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Klug, CA;Morrison, SJ;Weissman, IL
小鼠淋巴样细胞的产生依赖于Ikaros蛋白的功能，Ikaros被鉴定为一种淋巴限制的锌指转录因子，它来自于可选择的剪接消息，Ikaros基因敲除的小鼠在多个细胞谱系中存在缺陷，这引发了该蛋白是否调节多个承诺的祖细胞和/或多能干细胞的问题。为了解决这个问题，我们检测了多潜能细胞和更忠诚的祖细胞的纯化群体中Ikaros的表达，我们发现Ikaros的DNA结合亚型定位于最原始的造血干细胞亚群的核中。Ikaros的RNA剪接模式的变化发生在两个阶段：(I)随着长期的自我更新干细胞分化为短期的自我更新干细胞，以及(Ii)随着非自我更新的多能祖细胞分化为淋巴样承诺的祖细胞，我们意外地通过免疫金电子显微镜发现Ikaros在Abelson转化的Pre-B淋巴细胞中定位于异染色质，这些观察表明Ikaros在淋巴发育中扮演着复杂的角色。
The generation of lymphoid cells in mice depends on the function of the Ikaros protein, Ikaros has been characterized as a lymphoid-restricted, zinc-finger transcription factor that is derived from an alternatively spliced message, Ikaros knockout mice have defects in multiple cell lineages, raising the question of whether the protein regulates multiple committed progenitors and/or multipotent stem cells. To address this issue, we examined Ikaros expression in purified populations of multipotent cells and more committed progenitors, We found that the DNA-binding isoforms of Ikaros were localized in the nucleus of the most primitive hematopoietic stem cell subset. Changes in the RNA splicing pattern of Ikaros occurred at two stages: (i) as long-term self-renewing stem cells differentiated into short-term self-renewing stem cells and (ii) as non-self-renewing multipotent progenitors differentiated into lymphoid-committed progenitors, Unexpectedly, we found Ikaros localized to heterochromatin in Abelson-transformed pre-B lymphocytes by using immunogold electron microscopy, These observations suggest a complex role for Ikaros in lymphoid development.