TY - JOUR
T1 - Characterization of DNA Methylomic Signatures in Induced Pluripotent Stem Cells During Neuronal Differentiation
AU - Imm, Jennifer
AU - Pishva, Ehsan
AU - Ali, Muhammadd
AU - Kerrigan, Talitha L.
AU - Jeffries, Aaron
AU - Burrage, Joe
AU - Glaab, Enrico
AU - Cope, Emma L.
AU - Jones, Kimberley M.
AU - Allen, Nicholas D.
AU - Lunnon, Katie
N1 - Publisher Copyright:
© Copyright © 2021 Imm, Pishva, Ali, Kerrigan, Jeffries, Burrage, Glaab, Cope, Jones, Allen and Lunnon.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - EPIC array
KW - aging
KW - epigenetics
KW - epigenome-wide association study
KW - induced pluripotent stem cells
KW - neuronal differentiation
KW - trajectory inference
UR - http://www.scopus.com/inward/record.url?scp=85110240300&partnerID=8YFLogxK
U2 - 10.3389/fcell.2021.647981
DO - 10.3389/fcell.2021.647981
M3 - Article
AN - SCOPUS:85110240300
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 647981
ER -