Interestingly, neurons also showed a high expression of tyrosine hydroxylase (an enzyme that converts the amino acid tyrosine to the dopamine precursor) and consequently had increased production of norepinephrine and dopamine. HiPSCs derived from these patients had abnormal differentiation tendencies and differentiated neurons had reduced expression of genes marking lower cortical layers and callosal projection neurons. The same group later used a bioinformatics approach, integrating co-expression network analysis and transcription factor binding analysis, to provide mechanisms by which altered calcium signaling generates altered level of calcium-dependent transcriptional regulators leading to the transcriptional network changes observed in TS patient-derived neurons 113. Another group reported that hiPSC-derived neurons from individuals with Timothy syndrome have activity-dependent dendrite retraction 114. Both groups promisingly were able to partially reverse some of the deficits in TS patient-derived neurons.
