Fig. 2: MAPT p.R406W is sufficient to induce transcriptome-wide changes in iPSC-derived cortical neurons. | Translational Psychiatry

Fig. 2: MAPT p.R406W is sufficient to induce transcriptome-wide changes in iPSC-derived cortical neurons.

From: Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP

Fig. 2

a Fibroblasts from a symptomatic MAPT p.R406W carrier were reprogrammed into iPSC. CRISPR/Cas9 was used to correct the mutant allele and to establish an isogenic control line. iPSCs from MAPT p.R406W and isogenic controls were differentiated into cortical neurons and cultured for 6 weeks prior to analysis. b Digital deconvolution was applied to bulk RNA-seq data to define the relative percentage of neurons, astrocytes, microglia and oligodendrocytes. We demonstrate that MAPT p.R406W and isogenic control cultures are similarly enriched in neurons (>98%). Graph represents mean ± SEM. c Principal Component Analysis demonstrates that MAPT p.R406W is sufficient to induce transcriptome-wide differences in gene expression (PC1: 48% variance). d Differential expression analysis reveals that 328 genes differ between iPSC-derived cortical neurons carrying MAPT p.R406W vs. isogenic control (FDR B-Y < 0.05). Gene expression represented as in a heat map. RNA-seq was analyzed in 3 biological replicates

Back to article page