Are the gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy consistent with proposed mechanisms of pathogenesis?
Normal ABCD1 gene function is not required for reprogramming skin fibroblasts into iPSCs or maintaining pluripotency. Relative to DEGs found in fibroblasts, DEGs uncovered in comparisons of CCALD patient and control iPSCs are more consistent with major hypotheses regarding disease pathogenesis. These DEGs were independent of differences in sVLCFA levels, which did not vary according to ABCD1 mutation status. The highlighted genes provide new leads for pathogenic mechanisms that can be explored in animal models and human tissue specimens. We suggest that these iPSC resources will have applications that include assisting efforts to identify genetic and environmental modifiers and screening for therapeutic interventions tailored towards affected cell populations and patient genotypes.
These results suggest that envelope-related signals recorded in EEG data can be used to form robust auditory BCI's that do not require artificial manipulation (e.g., amplitude modulation) of stimuli to function.