Frontiers in Cell and Developmental Biology (Jul 2021)

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

  • Jennifer Imm,
  • Ehsan Pishva,
  • Ehsan Pishva,
  • Muhammadd Ali,
  • Talitha L. Kerrigan,
  • Aaron Jeffries,
  • Joe Burrage,
  • Enrico Glaab,
  • Emma L. Cope,
  • Kimberley M. Jones,
  • Nicholas D. Allen,
  • Katie Lunnon

DOI
https://doi.org/10.3389/fcell.2021.647981
Journal volume & issue
Vol. 9

Abstract

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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.

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