Table 5.
Major methods and findings on COS associated CNVs and on COS.
| Ref | Major Methods | Major Findings on COS and Associated CNVs |
|---|---|---|
| [73] | Microarray, WCPC | Delayed decline of pluripotency markers in AOS with 22q11.2 |
| [74] | WCPC, single cell Ca2+ imaging and PCR | Dysregulation of genes relevant to GABAergic, glutamatergic, and dopaminergic in electrical active neurons |
| [75] | Whole genome sequencing, postmortem brain | Increased L1 retrotransposition in postmortem brain from patients with AOS and iPSC derived neurons from AOS patients with 22q11.2 deletion |
| [76] | MicroRNA profiling | 32 miRNAs are upregulated in neurons with 22q11.2 microdeletion, miRNA deregulation is broadly shared across AOS, SAD, and COS |
| [77] | Paired-end mRNA sequencing | Perturbed neuronal MAPK signaling, differentially expressed genes from the 22q11.2 microdeletion act during critical periods of development |
| [78] | miRNA and mRNA arrays | Reduced neurosphere size, neural differentiation, neurite outgrowth, cellular migration, and expression of miR-17/92 cluster and miR-106a/b that inhibit p38a (MAPK14) expression, p38 inhibitors improve diminished neurogenic-to-gliogenic ratio |
| [79] | ICC/IHC, complementation and knock-down experiments | Defects in adherens junctions and apical polarity. Displacement of radial glia cells leads to cortical malformation during mouse development |
| [80] | ICC, IB | Lower expression of CYFIP1 and PSD-95, altered dendritic morphology |
| [81] | Gene editing, iNeurons, electrophysiology | Reduced spontaneous mEPSC frequency, but not amplitude, and decrease in evoked EPSC amplitude. Unaltered electrical properties of human neurons, synapse numbers, and dendritic arborization |
| [82] | Histomorphology, electro-physiology | 16p del- and 16p dup-derived NPCs show opposing differences in soma size and arborization, reduced excitability in 16p del-derived neurons, increased potassium current density in 16p dup-derived neurons, lower density of excitatory synapses in 16p del- and 16p dup-derived neurons associates with increased amplitude of mEPSCs |
| [83] | digital miRNA profiling | Downregulation of miR-9, a regulator of neurogenesis and of radial migration |
| [84] | IB, IHC, IP, knock-down | Increased STEP61 protein expression in forebrain neurons impairs NMDAR signaling |
| [85] | mRNA sequencing | Transcriptional signatures of NPCs and neurons show concordance with postmortem case/control brain samples from SCZ, BP, and ASD after adjusting for cell type composition |
Abbreviations are: AOS, Adult Onset Schizophrenia; ASD, Autism Spectrum Disorder; BP, Bipolar Disorder; COS, Childhood Onset SCZ; IB, immunoblot; ICC, immunocytochemistry; IHC, immunohistochemistry; IP, immunoprecipitation; mEPSC, miniature excitatory postsynaptic current; NPC, neuronal progenitor cell; WCPC, whole cell patch clamp.