Characterization of DNA Methylomic Signatures in Induced Pluripotent Stem Cells During Neuronal Differentiation

• Main Authors: Jennifer Imm, Ehsan Pishva, Muhammadd Ali, Talitha L. Kerrigan, Aaron Jeffries, Joe Burrage, Enrico Glaab, Emma L. Cope, Kimberley M. Jones, Nicholas D. Allen, Katie Lunnon
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-07-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: aging; DNA methylation; EPIC array; epigenetics; epigenome-wide association study; induced pluripotent stem cells
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2021.647981/full

In development, differentiation from a pluripotent state results in global epigenetic changes, although the extent to which this occurs in induced pluripotent stem cell-based neuronal models has not been extensively characterized. In the present study, induced pluripotent stem cell colonies (33Qn1 line) were differentiated and collected at four time-points, with DNA methylation assessed using the Illumina Infinium Human Methylation EPIC BeadChip array. Dynamic changes in DNA methylation occurring during differentiation were investigated using a data-driven trajectory inference method. We identified a large number of Bonferroni-significant loci that showed progressive alterations in DNA methylation during neuronal differentiation. A gene–gene interaction network analysis identified 60 densely connected genes that were influential in the differentiation of neurons, with STAT3 being the gene with the highest connectivity.