Lithium reverses the imbalance in the proliferation and differentiation of MARK2 mutant iPSC-derived NPCs by activating the WNT/β-catenin signaling pathway
(A) Representative immunofluorescence images of ZO1 (green) and TUJ1 (red) in different iPSC-derived neural rosettes. CTRL1 and CTRL2, 2 independent healthy adults without MARK2 variant; p.C723Sfs and p.F271Sfs, 2 affected individuals with LOF MARK2 variants; and CRISPR-Del1 and CRISPR-Del2, 2 isogenic MARK2 deletions produced by the CRISPR-Cas9 editing technology. Both CRISPR-Del and mutant iPSC-derived neural rosettes were treated with LiCl (0.7 mM) or rhWNT3A (100 ng/mL).
(B) Representative immunofluorescence images of Ki67 (green) and BrdU (red) in different iPSC-derived NPCs.
(C) Representative immunofluorescence images of TUJ1 (green) and DCX (red) in different iPSC-derived NPCs. Scale bar = 50 μm. The quantification and statistical analysis were showed in Figure S7.