scholarly journals MicroRNA Alterations in Induced Pluripotent Stem Cell-Derived Neurons from Bipolar Disorder Patients: Pathways Involved in Neuronal Differentiation, Axon Guidance, and Plasticity

2020 ◽  
Vol 29 (17) ◽  
pp. 1145-1159 ◽  
Author(s):  
Monica Bame ◽  
Melvin G. McInnis ◽  
K. Sue O'Shea
Author(s):  
Jennifer Imm ◽  
Ehsan Pishva ◽  
Muhammadd Ali ◽  
Talitha L. Kerrigan ◽  
Aaron Jeffries ◽  
...  

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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