Fig. 4.

Ectopic TDP-43 expression partially reproduces the iPSC phenotype. (A) Representative images of cytoplasmic and nuclear-only TDP43:mApple-transfected astrocytes showing the criteria for inclusion of astrocytes in either cytoplasmic (Upper) or nuclear (Lower). (B) Analysis of exogenous WT TDP-43 localization on stratified relative expression groups. The localization of WT TDP-43 was significantly related to relative expression levels [nuclear vs. cytoplasmic TDP-43: A, not significant (n.s.); B, n.s.; C, n.s.; D, P < 0.05; E, P < 0.01; F, P < 0.001). Data are pooled from three independent experiments. (C) Analysis of exogenous M337 TDP-43 localization on stratified relative expression groups. M337V TDP-43 remained localized mainly to the cytoplasm regardless of expression level (nuclear vs. cytoplasmic TDP-43: A–F, P < 0.001). Data are pooled from three independent experiments. (D) Comparison of ectopic TDP-43 localization in astrocytes from the lowest relative expression level groups (group A in B and C). At low expression levels, 73.6 ± 3.3% of astrocytes from the TDP43^M337V:mApple group presented mainly or exclusively cytoplasmic localization of the protein, compared with 44.5 ± 1.6% in the TDP43^WT:mApple. **P < 0.01; ***P < 0.001 (one-way ANOVA).