Figure 1

Generation of iPSCs from FTLD-Tau patients with either intronic or exonic MAPT mutation and gene editing for isogenic control.

(a) iPSCs generated from familial FTLD-Tau patients with a MAPT mutation showed ESCs-like morphology (phase image) and expressed the pluripotent stem cell markers SSEA4 and Nanog. Scale bar = 100 μm. (b) The FTLD-Tau1 iPSC line carried a MAPT intron mutation (intron 10 + 14C → T), and the FTLD-Tau2 iPSC line carried a MAPT exon mutation (R406W). (c,d) The mutation in FTLD-Tau1 was corrected (FTLD-Tau1 corrected) using the CRISPR/Cas9 system. Sanger sequence analysis revealed correction of the mutation after gene editing. (e) RT-PCR showing FTLD-Tau1 neurons with increased 4 repeat tau expression, and FTLD-Tau1 corrected neurons with the normal expression ratio of 4 repeat and 3 repeat tau. Full-length picture of the gel is presented in Figure S4(a). (f) Cell lysates were dephosphorylated with lambda phosphatase and separated by SDS-PAGE for comparison with recombinant tau ladder followed by detection using an anti-total tau antibody (Tau12). Altered band pattern of FTLD-Tau1 was reversed in FTLD-Tau1 corrected. Full-length picture of the blot is presented in Figure S4(b).