Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.
Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.
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DOI：
10.1016/j.stem.2016.03.012
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发表时间：
2016-05-05
期刊：
影响因子：
23.9
通讯作者：
Kriegstein AR
中科院分区：
文献类型：
--
作者：
Nowakowski TJ;Pollen AA;Di Lullo E;Sandoval-Espinosa C;Bershteyn M;Kriegstein AR
最近在巴西爆发的寨卡病毒（ZIKV）与胎儿畸形和小头畸形的大幅增加有关。然而，有关病毒感染与这些缺陷相关的潜在分子和细胞机制的信息仍然有限。在这项研究中，我们已经检查了涉及几种包膜病毒（包括ZIKV）进入细胞的受体在发育中的大脑中跨不同细胞类型的表达。使用单细胞RNA-Seq和免疫组织化学，我们发现候选病毒进入受体AXL在发育中的人皮质中由人放射状胶质细胞、星形胶质细胞、内皮细胞和小胶质细胞高度表达，并且在发育中的视网膜中由祖细胞高度表达。我们还表明，放射状神经胶质细胞中的AXL表达在发育中的小鼠和雪貂皮层以及人类干细胞衍生的脑类器官中是保守的，突出了可用于研究ZIKV感染性机制和对大脑发育影响的多个实验系统。
The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single cell RNA-Seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex, and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex, and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development.