HiPSC models from RTT patients with rarer mutations have also been created. Groups have derived hiPSCs and neurons from RTT patients with CDKL5 and FOXG1 mutations showing reduced number of synaptic contacts, aberrant spine structures, increased tendency to differentiate into inhibitory synapses, and reduced excitatory synaptic markers 85,87–89. Other studies modeling Rett Syndrome 90,91 have differentiated hiPSCs into astrocytes, supporting cells that form and maintain the environment and microstructure for neurons, and suggested that mutant RTT astrocytes have adverse effects on the morphology and function of WT neurons, which were partially rescuable with IGF1 treatment. Globally, the evidence suggests that Rett is a non-cell autonomous disorder (disorder in which genotypically mutant cells causes other non-genotypically mutant cells to exhibit a mutant phonetype) and that the glial effect on neuronal morphology is separate from the intrinsic neuronal deficit in RTT mutant neurons. Delepine et al. found that microtube-dependent vesicle transport in mutant astrocytes was altered and they were able to reverse this with Epothilone D 90.
