Table 4.
Major analytical methods and findings in iPSC-based case/control studies in SCZ.
| Ref. | Major Methods | Major Findings in SCZ iPSCs Derived Cells |
|---|---|---|
| [75] | Rabies virus transport, electrophysiology, calcium transients, microarray | Reduced neuronal connectivity, maintained synaptic function, altered gene expression in glutamate, cAMP, BMP, and WNT pathways; loxapine application normalizes alterations |
| [76] | Potassium-induced depolarization, RNA-seq | Reduced activity-dependent transcription, coexpression modules are enriched for GWAS risk variants |
| [77] | RNA-seq, reporter assay | Differentially expressed genes from WNT, SHH, BMP, and G-protein coupled signaling |
| [78] | Cell imaging, HPLC, mitochondrial assays | Impaired dopaminergic differentiation and glutamatergic maturation, mitochondria show reduced membrane potential, respiration, and connectivity, and uneven network structure |
| [79] | Potassium-induced depol-arization, HPLC, ICC | Increased basal and activity-dependent cortical secretion of dopamine, epinephrine, and norepinephrine |
| [80] | ICC | SCZ/control-iPSCs differentiate equally well into FOXA2-positive midbrain dopaminergic neurons |
| [81] | WCPC, calcium transients | Delayed differentiation of NPCs into DG-like neurons, reduced spontaneous neurotransmitter release |
| [82] | RNA-seq, SCS, WCPC, MEA | Reduced spontaneous spike and network bursts in mature, but not in early, SCZ iPSC-DG-CA3 circuits |
| [83] | Oxygen consumption, ROS production | Increased extra-mitochondrial oxygen consumption and ROS production that is normalized by valproate |
| [70] | Microarray, mass spectrometry | Abnormal gene and protein expression related to cytoskeletal remodeling and oxidative stress, impaired NPC migration, differentiation, and mitochondrial membrane potential, and increased ROS levels |
| [84] | Mitochondria transfer | Improved mitochondrial function and glutamatergic differentiation following mitochondria transfer |
| [85] | Expression studies in iNs, electrophysiology | miR-137 downregulates presynaptic plasticity genes and vesicle secretion in iNs |
| [55] | ATAC-seq, gene editing, SCS | Modification to a non-risk allele increases MIR137 expression and reduces neuronal maturation |
| [86] | Nanostring, RNA-seq, mass spectrometry | Reduced miR-9 expression inhibits outgrowth migration of NPC neurospheres |
| [87] | RNA-Seq, small RNA-seq, ChIP-Seq | Increased expression of miRNA networks, impaired miRNA dependent gene regulation |
Abbreviations are: ATAC-seq, sequencing assay for transposase-accessible chromatin; BMP, bone morphogenetic proteins; ChIP-Seq, chromatin immunoprecipitation sequencing; iN, induced neurons; HPLC, high pressure liquid chromatography; ICC, immunocytochemistry; MEA, multiple-electrode array; Nanostring, digital expression profiling; NPC, neuronal progenitor cell; RNA-seq, RNA sequencing; ROS, reactive oxygen species; SHH, sonic hedgehog; SCS, single cell sequencing; WCPC, whole cell patch clamp; WNT, Wingless.