Blood:Hif-1α和Hif-2α参与调控血管内皮和造血干细胞的形成。

2018-01-17 MedSci MedSci原创

在发育过程中,造血干细胞(HSCs)是通过内皮细胞-造血性转变(EHT),由特殊的内皮细胞衍生而来,称为血管内皮细胞(HE)。已有报道体内缺氧诱导因子-1α(HIF-1α)可正性调控EHT,现研究人员对该过程可能存在其他的调控因子进行探究。Claudia Gerri等人发现,斑马鱼的Hif-2α也可以正性调控HSC形成。在携带hif-1aa;hif-1ab(hif-1α)和hif-2aa;hif-

在发育过程中,造血干细胞(HSCs)是通过内皮细胞-造血性转变(EHT),由特殊的内皮细胞衍生而来,称为血管内皮细胞(HE)。

已有报道体内缺氧诱导因子-1α(HIF-1α)可正性调控EHT,现研究人员对该过程可能存在其他的调控因子进行探究。

Claudia Gerri等人发现,斑马鱼的Hif-2α也可以正性调控HSC形成。在携带hif-1aa;hif-1ab(hif-1α)和hif-2aa;hif-2ab(hif-2α)突变的斑马鱼和吗啡啉突变体中,HSC标志性基因表达量明显下调。通过实时成像,研究人员发现hif-1α和hif-2α还在HE规范化过程中发挥正性调控作用。

敲除hif-1α突变体的hif-2α会导致HSC形成进一步减少,提示hif-1α和hif-2α在EHT的调控上有部分相同的作用。而且,可明显刺激野生型动物HSC形成增加的低氧环境,对hif-1α和hif-2α功能双缺失的动物几乎没有影响。另外,研究人员还发现Hif和Notch都参与EHT的上游信号通路。Notch1a和notch1b突变体表现为EHT受损,而且不能被低氧挽救。

但在ECs中过表达Notch的胞内结构域可有效挽救hif-1α和hif-2α吗啡啉突变体的EHT表现,表明在HSC形成过程中,Notch信号是在Hif通路的下游发挥作用。

总而言之,本研究证明了hif-1α、hif-2α和Notch均参与EHT的上游信号通路,且hif-1α和hif-2α在Notch的上游。

原始出处:

Claudia Gerri,et al.Hif-1α and Hif-2α regulate hemogenic endothelium and hematopoietic stem cell formation in zebrafish.Blood  2018  :blood-2017-07-797795;  doi: https://doi.org/10.1182/blood-2017-07-797795

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    2018-01-22 brillianter

    不错.学习了

    0

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    2018-01-22 brillianter

    不存

    0

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    2018-01-22 brillianter

    0

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    2018-01-19 俅侠
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    2018-01-19 changfy
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    2018-01-19 wrj0126

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