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Blood：缺铁促进巨核系-红系祖细胞（MEP）向巨核细胞系偏倚进展

2019-08-28 MedSci MedSci原创

缺铁血小板贫血MEP
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缺铁性贫血患者血小板增多的机制尚不清楚。有这样一种假设，即低铁会促进巨核系-红系祖细胞（MEP）向巨核细胞（Mk）系偏倚进展。Xavier-Ferrucio等人在人和小鼠中证实了该假设。与野生型（WT）小鼠的MEP相比，在表现为缺铁性贫血和血小板增多症的特异性敲除跨膜丝氨酸蛋白酶6(Tmprss6-/-)小鼠的MEP中，研究人员观察到Mk偏倚、不稳定铁减少和增殖减少。骨髓移植实验显示是系统性铁缺乏

缺铁性贫血患者血小板增多的机制尚不清楚。有这样一种假设，即低铁会促进巨核系-红系祖细胞（MEP）向巨核细胞（Mk）系偏倚进展。Xavier-Ferrucio等人在人和小鼠中证实了该假设。

与野生型（WT）小鼠的MEP相比，在表现为缺铁性贫血和血小板增多症的特异性敲除跨膜丝氨酸蛋白酶6(Tmprss6-/-)小鼠的MEP中，研究人员观察到Mk偏倚、不稳定铁减少和增殖减少。骨髓移植实验显示是系统性铁缺乏（而非造血细胞Tmprss6敲除的局部作用)导致了在Tmprss6-/-小鼠中所观察到的MEP谱系分化偏倚。获得性缺铁性贫血的非转基因小鼠也表现为血小板增多和Mk偏倚性MEP。

基因表达分析显示，与WT MEP相比，在Tmprss6-/- MEP中，编码代谢、VEGF和ERK通路相关基因的mRNA富集表达。敲低转铁蛋白受体2后，人类原代MEP也表现出增殖减少和Mk偏倚分化，与缺铁性贫血小鼠模型中的表现一致。信号转导分析表明，缺铁时，人和小鼠MEP的磷酸化-ERK1/2水平均低于对照组。

本研究结果与另一个小鼠模型（骨髓环境低铁，影响MEP代谢、减弱ERK信号、减缓增殖，并使MEP向Mk细胞系偏倚分化）的结果一致。

原始出处：

Juliana Xavier-Ferrucio， et al.Low Iron Promotes Megakaryocytic Commitment of Megakaryocytic-Erythroid Progenitors in Humans and Mice.Blood 2019 ：blood.2019002039； doi： https：//doi.org/10.1182/blood.2019002039

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    2019-08-30 luckyshitiancai_42705684

    #缺铁#

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    2019-08-30 liuquan

    #巨核细胞#

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    2019-08-30 12498636m52(暂无昵称)

    #祖细胞#

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    2019-08-30 zhangxingru

    #细胞系#

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