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首页> 外文期刊>Nature immunology >The E3 ligase Itch is a negative regulator of the homeostasis and function of hematopoietic stem cells.
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The E3 ligase Itch is a negative regulator of the homeostasis and function of hematopoietic stem cells.

机译：E3连接酶Ich是造血干细胞稳态和功能的负调节剂。

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摘要

Although hematopoietic stem cells (HSCs) are the most thoroughly characterized type of adult stem cell, the intricate molecular machinery that regulates their self-renewal properties remains elusive. Here we showed that the E3 ubiquitin ligase Itch negatively regulated the development and function of HSCs. Itch(-/-) mice had HSCs with enhanced frequency, competence and long-term repopulating activity. Itch-deficient HSCs showed accelerated proliferation rates and sustained progenitor properties, as well as more signaling by the transcription factor Notch1, due to more accumulation of activated Notch1. Knockdown of Notch1 in Itch-mutant HSCs resulted in reversion of the phenotype. Thus, we identify Itch as a previously unknown negative regulator of HSC homeostasis and function.
机译：尽管造血干细胞（HSC）是成年干细胞中最全面表征的类型，但调节其自我更新特性的复杂分子机制仍然难以捉摸。在这里，我们显示E3泛素连接酶Itch负调控HSC的发育和功能。瘙痒（-/-）小鼠的HSC的频率，能力和长期繁殖活性均增强。缺痒的HSCs显示出加速的增殖速率和持续的祖细胞特性，以及由于激活的Notch1的更多积累而导致的转录因子Notch1的更多信号传导。在痒突变HSCs中Notch1的基因敲低导致该表型的回复。因此，我们确定Itch是HSC稳态和功能的一个未知的负调节剂。

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