Figure 4.

Loss of UTX Results in Decreased Neurite Complexity and Electrophysiological Defects of hESC-Derived Neurons

(A) Representative images of neurons derived from UTX WT and KO hESCs at day 40 of neural differentiation.

(B) Sholl analysis showing that total neurite length reduced in UTX KO hESC-derived neurons (60 neurons in every group in 3 independent experiments).

(C–E) Compared with WT group, UTX KO hESC-derived neurons exhibited decreased dendritic complexity as shown in reduced numbers of intersections (C), nodes (D), and ends (E).

(F) Representative traces of membrane potential responding to step depolarization by current injection steps from −10 pA to +60 pA in 10-pA increments. Membrane potential was current-clamped at around -65 mV. Representative traces were displayed by WT neurons.

(G) Quantification of the neuron maturity by recorded AP firing patterns at day 60 after differentiation (more than 15 neurons in every group have been recorded).

(H) Representative traces of whole-cell currents in voltage-clamp mode. Cells were held at −70 mV. Step depolarization from −80 to +60 mV at 10-mV intervals was delivered. Inset shows Na⁺ currents.

(I) Quantification of membrane capacitance in neurons at 60 days after differentiation. Error bars indicate ±SEM. ^∗p < 0.05; a two-tailed t test was performed.

(J) Quantification of membrane resistance in neurons at 60 days after differentiation. ^∗p < 0.05.

(K and L) Averaged current-voltage relationship (I-V curves) for Na⁺ currents, recorded from hESC-derived neurons. ns, not significant; ^∗p < 0.05, ^∗∗p < 0.01.

(M and N) Averaged current-voltage relationship (I-V curves) for K⁺ currents, recorded from hESC-derived neurons. ns, not significant; ^∗p < 0.05, ^∗∗p < 0.01.