Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Epigenomics. 2019 Aug;11(10):1143-1161. doi: 10.2217/epi-2018-0180. Epub 2019 Jun 25.
This study was aimed to understand if Zika virus (ZIKV) alters the DNA methylome of human neural progenitor cells (hNPCs). Whole genome DNA methylation profiling was performed using human methylationEPIC array in control and ZIKV infected hNPCs. ZIKV infection altered the DNA methylation of several genes such as WWTR1 (TAZ) and RASSF1 of Hippo signaling pathway which regulates organ size during brain development, and decreased the expression of several centrosomal-related microcephaly genes, and genes involved in stemness and differentiation in human neural progenitor cells. Overall, ZIKV downregulated the Hippo signaling pathway genes which perturb the stemness and differentiation process in hNPCs, which could form the basis for ZIKV-induced microcephaly.
本研究旨在探讨寨卡病毒(ZIKV)是否改变了人神经祖细胞(hNPCs)的 DNA 甲基化组。在对照和感染 ZIKV 的 hNPCs 中使用人类甲基化 EPIC 芯片进行全基因组 DNA 甲基化分析。ZIKV 感染改变了 Hippo 信号通路中几个基因的 DNA 甲基化,如 WWTR1(TAZ)和 RASSF1,该通路在大脑发育过程中调节器官大小,并且降低了几个中心体相关小头畸形基因以及与 hNPCs 中的干性和分化相关的基因的表达。总体而言,ZIKV 下调了 Hippo 信号通路基因,破坏了 hNPCs 中的干性和分化过程,这可能是 ZIKV 引起小头畸形的基础。