EFFECTS OF MATERNAL FACTORS ON DNA METHYLATION PATTERN IN HUMAN NEURAL PROGENITOR CELLS

Abstract

This study aimed at understanding the effects of maternal factors i.e., High glucose (HG) and Zika virus (ZIKV) infection on DNA methylation patterns in human neural progenitor cells (hNPCs).

HG exposure of hNPCs was found to alter the DNA methylation pattern of genes involved in axon guidance (SLIT1-ROBO2 signalling), and Hippo signalling (YAP/TAZ) resulting in their decreased gene expression. Furthermore, SLIT1 knockdown in hNPCs downregulated the expression of its downstream effectors and TAZ, suggesting HG perturbs the cross-talk between SLIT1-ROBO2 and Hippo signalling, thereby causing neurological disorders.

ZIKV infection altered DNA methylation of Hippo signalling genes and decreased the expression of several centrosomal-related microcephaly genes, and genes involved in stemness and differentiation in hNPCs indicating ZIKV downregulated the Hippo signalling genes which perturb the stemness and differentiation process in hNPCs. Taken together, this study demonstrated the possible molecular and epigenetic mechanisms by which maternal factors (HG/ZIKV) contribute to neurological disorders.