TABLE 5

Overview of organotypic tissue cultures for cerebral disease modeling

DiseaseGeneCellsProtocolPhenotypeReference
Micro-cephalyCDK5RAP2hiPSCsCerebral cortexSmaller neuroepithelial regions, altered spindle orientation of radial glial cells, abundant neuronal outgrowth, smaller organoid size.(Lancaster et al., 2013)
Seckel syndromeCPAPhiPSCsCerebral cortexExtended G1‐S transition in NPCs from Seckel cell patient iPSCs. Premature NPC differentiation resulting in reduced cell number.(Gabriel et al., 2016)
Macro-cephalyPTENhESCsCerebral cortexPromoted cell cycle re-entry and delayed neuronal differentiation, resulting in a pronounced expansion of the radial glia and intermediate progenitor cells and increased organoid size.(Li et al., 2017)
Autism spectrum disorderhiPSCsDorsal telencephalonAbnormal proliferation of neural progenitor cells and an increased production of inhibitory GABAergic neurons, enhanced FOXG1 expression(Mariani et al., 2015)
SchizophreniaDISC1hiPSCsForebrainProlongs mitotic length and cell-cycle deficits in radial glial cells(Ye et al., 2017)
SchizophreniaFGFR1hiPSCs and hESCsCerebral cortexDisorganized migration of proliferating cells and depletion of cortical neurons. Cortical malformation and altered FGFR1 signaling.(Stachowiak et al., 2017)
SchizophreniahiPSCsDorsal forebrainDifferential expression of genes involved in synaptic biology and neurodevelopment. Subdued responses to stimulation and depolarization. Mitochondrial functional defects.(Kathuria et al., 2020)
Alzheimer diseasehiPSCsCortexGeneration of pathologic amyloid β peptides(Lee et al., 2016)
Alzheimer diseaseAPPhiPSCsNeocortexβ-amyloid aggregation, hyperphosphorylated τ, endosome abnormalities(Raja et al., 2016)
Alzheimer diseasehiPSCsTriculture of neurons, astrocytes, and microgliaIncreased Aβ aggregation, phosphorylated τ accumulation, neuroinflammatory activity, and microglia recruitment(Park et al., 2018)
Parkinson diseaseLRRK2hiPSCsMidbrainIncreased aggregation of α-synuclein and decreased dopaminergic neurite length(Kim et al., 2019)
Miller-Dieker syndromehiPSCsForebrainIncreased apoptosis and horizontal divisions in neural stem cells, mitotic delay in outer radial glia-like cells(Bershteyn et al., 2017)
Miller-Dieker syndromeLIS1hiPSCsForebrainSmaller organoids with fewer neuroepithelial loops, fewer symmetric ventricular radial glia cells divisions, disrupted cortical niche(Iefremova et al., 2017)
Rett syndromeMeCP2hiPSCsUndefinedAberrant neurogenesis and neuronal differentiation, increased ventricular area, and decreased radial thickness of organoid(Mellios et al., 2018)
ZIKA virus infectionZIKVhiPSCsForebrainSuppression of neural progenitor cell proliferation, decreased neuronal layer thickness and organoid size, enlarged lumen/ventricles(Qian et al., 2016)
ZIKA virus infectionZIKVhESCsCerebral cortexZIKV-mediated TLR3 activation, reduction in organoid volume resembling microcephaly.(Dang et al., 2016)
ZIKA virus infectionZIKV-NS2AhiPSCsForebrainZIKV-NS2A impairs radial glial cell proliferation and adherens junction formation(Yoon et al., 2017)
  • hESC, human embryonic stem cell.