Nox2 contributes to the arterial endothelial specification of mouse induced pluripotent stem cells by upregulating Notch signaling.
Nox2 contributes to the arterial endothelial specification of mouse induced pluripotent stem cells by upregulating Notch signaling.
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Nox2 通过上调 Notch 信号传导促进小鼠诱导多能干细胞的动脉内皮规范
DOI：
10.1038/srep33737
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发表时间：
2016-09-19
影响因子：
4.6
通讯作者：
Meng D
中科院分区：
文献类型：
--
作者：
Kang X;Wei X;Wang X;Jiang L;Niu C;Zhang J;Chen S;Meng D
活性氧簇(ROS)在干细胞分化中起着至关重要的作用，然而，ROS调节干细胞向内皮细胞分化的机制尚不清楚。在这里，我们确定了NADPH氧化酶2(NOX2)产生的ROS在小鼠诱导多能干细胞(MiPSCs)内皮谱系规范中的作用。当野生型(WT)和NOX2基因敲除(NOX2MIPCSCs)分化为内皮细胞(−/−-ECs)时，NOX2−/−细胞的内皮标志物、动脉内皮细胞标志物、促血管生成细胞因子和Notch通路成分的表达受到抑制，而WT和NOX2NOX2miPSCs的表达则随着NOX2表达上调而增加。较高水平的NOX2表达增加了Notch信号和动脉内皮细胞分化，这种增加可被抑制ROS的产生或沉默Notch1的表达所消除。NOX2缺乏可导致小鼠缺血肢体微血管内皮细胞存活率和血管生成能力下降，−/−组小鼠缺血肢体毛细血管密度和动脉密度低于WTmiPSC-EC组。综上所述，这些观察表明，NOX2介导的ROS的产生通过激活Notch信号通路促进动脉内皮细胞分化为miPSCs，并有助于移植的miPSC来源的ECs的血管生成能力。
Reactive oxygen species (ROS) have a crucial role in stem-cell differentiation; however, the mechanisms by which ROS regulate the differentiation of stem cells into endothelial cells (ECs) are unknown. Here, we determine the role of ROS produced by NADPH oxidase 2 (Nox2) in the endothelial-lineage specification of mouse induced-pluripotent stem cells (miPSCs). When wild-type (WT) and Nox2-knockout (Nox2−/−) miPSCs were differentiated into ECs (miPSC-ECs), the expression of endothelial markers, arterial endothelial markers, pro-angiogenic cytokines, and Notch pathway components was suppressed in the Nox2−/− cells but increased in both WT and Nox2−/− miPSCs when Nox2 expression was upregulated. Higher levels of Nox2 expression increased Notch signaling and arterial EC differentiation, and this increase was abolished by the inhibition of ROS generation or by the silencing of Notch1 expression. Nox2 deficiency was associated with declines in the survival and angiogenic potency of miPSC-ECs, and capillary and arterial density were lower in the ischemic limbs of mice after treatment with Nox2−/− miPSC-ECs than WT miPSC-EC treatment. Taken together, these observations indicate that Nox2-mediated ROS production promotes arterial EC specification in differentiating miPSCs by activating the Notch signaling pathway and contributes to the angiogenic potency of transplanted miPSC-derived ECs.
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影响因子：
5.3
作者：
Coant, Nicolas;Ben Mkaddem, Sanae;Ogier-Denis, Eric
通讯作者：
Ogier-Denis, Eric
影响因子：
3.6
作者：
Baehner, RL;Millar-Groff, S;Bringas, P
通讯作者：
Bringas, P
影响因子：
--
作者：
Caliceti C;Nigro P;Rizzo P;Ferrari R
通讯作者：
Ferrari R
DOI：
10.1161/atvbaha.114.303218
发表时间：
2014-11-01
影响因子：
8.7
作者：
Corada, Monica;Morini, Marco Francesco;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta
影响因子：
20.1
作者：
Lassègue B;San Martín A;Griendling KK
通讯作者：
Griendling KK