|
| Disease | Studies | Organoid type | Methods of generation | outcomes |
|
| Primary microcephaly | Lancaster et al., 2013 [14] | Cerebral organoids | Patient iPSC-derived; CDK5RAP2 mutation | Fewer progenitor cells, premature neuronal differentiation; CDK5RAP2 overexpression rescued the mutant phenotypes |
| Li et al., 2017 [70] | Cerebral organoids | Patient iPSC-derived; ASPM mutation | Reduced organoid size, fewer progenitor cells in VZ and oSVZ, poor lamination, reduced neuronal calcium activity |
| Gabriel et al., 2016 [75] | Cerebral organoids | Seckel patient iPSC-derived; CPAP mutation | Delayed cilia disassembly led to premature differentiation of NPCs and reduced progenitor pools |
| Zhang et al., 2019 [134] | Cerebral organoids | hPSC-derived; CRISPR/Cas9-mediated homozygous knockout of WDR62 | Delayed cilia disassembly and retarded cell cycle progression led to reduced proliferation and premature differentiation of NPCs |
|
| Autism spectrum disorder (ASD) | Mariani et al., 2015 [15] | Cortical organoids | Idiopathic ASD patient iPSC-derived | Altered transcriptomic profiles, particularly FOXG1 upregulation; accelerated cell cycles; increased GABAergic neuron production, can be rescued by RNAi-mediated FOXG1 knockdown |
| Wang et al., 2017 [76] | Cerebral organoids | hiPSC-derived, CRISPR/Cas9-mediated heterozygous mutation of CHD8 (CHD8+/-) | Upregulation of genes involved in neurogenesis, neuronal differentiation, forebrain development, Wnt/β-catenin signaling, and axonal guidance |
|
| Tuberous sclerosis complex (TSC) | Blair et al., 2018 [81] | Cortical spheroids | CRISPR/Cas9-mediated homozygous knockout of TSC1 or TSC2 in hESCs | mTORC1 hyperactivation, reduced neurogenesis, increased gliogenesis; dysplastic cells in TSC2-/- cortical spheroids can be rescued by early and continuous rapamycin treatments |
|
| Neonatal hypoxia-ischemia injury | Boisvert et al., 2019 [82] | Cerebral organoids | hESC-derived; 72-hour under hypoxic environment | Inhibition of dorsal-related genes such as FOXG1, CTIP2, and TBR1; could be alleviated by minocycline |
| Pasca et al., 2019 [84] | Cortical spheroids | hiPSC-derived; 48-hour under hypoxic environment | Reduction of TBR2+ intermediate progenitors led to cell cycle damage and premature neural differentiation; rescued by ISRIB treatments |
|
| ZIKV-associated microcephaly | Qian et al., 2016 [17] | Cortical organoids | hiPSC-derived; MR766 and FSS13025 ZIKV strain infected | Reduced organoid size, reduced neuronal layer thickness, expanded ventricular lumen, increased cell death |
| Dang et al., 2016 [87] | Cerebral organoids | hESC-derived; MR766 ZIKV strain infected | Reduced organoid size, TLR3 upregulation and TLR3-mediated transcriptomic alterations; direct inhibition of TLR3 reduced phenotypes |
| Watanabe et al., 2017 [88] | Cortical organoids | hPSC-derived; PRVABC59 ZIKV strain infected | Activated innate immune responses led to increased progenitor apoptosis and reduced organoid size; duramycin or ivermectin rescued the teratogenic effects of ZIKV infection |
|
| SARS-CoV-2-associated neurological deficits | Jacob et al., 2020a [98] | Cortical, hippocampal, hypothalamic, midbrain, and ChP organoids | hiPSC-derived; SARS-CoV-2 USA-WA1/2020 infected | Particular tropism for ChP epithelial cells, caused increased cell death, transcriptional dysregulation, disrupted ChP epithelial integrity and barrier function |
| Pellegrini et al., 2020 [100] | Cerebral and ChP organoids | hPSC-derived; SARS-CoV-2 spike pseudovirus and live virus infected | Particular tropism for ChP epithelial cells of cerebral organoids; infected cells expressing ACE2 and lipoproteins; ChP epithelial integrity and barrier function were disrupted |
|
| Alzheimer’s disease (AD) | Gonzalez et al., 2018 [102] | Cerebral organoids | Familial AD or DS patient iPSC-derived | β-Amyloid (Aβ) aggregation, formation of neurofibrillary tangle-like structures, hyperphosphorylated tau, increased cell apoptosis |
| Lin et al., 2018 [109] | cerebral organoids | CRISPR/Cas9-generated isogenic iPSC lines homozygous for APOE4 alleles | Increased Aβ accumulation and tau phosphorylation |
|
| Parkinson’s disease (PD) | Kim et al., 2019a [34] | Midbrain organoids | CRISPR/Cas9-generated isogenic iPSC lines harboring LRRK2 G2019S mutation | Shortened neurite length and decreased marker expression of mDAN; increased aggregation and abnormal clearance of α-synuclein; inhibition of upregulated TXNIP ameliorated mutant phenotypes |
| Wulansari et al., 2021 [114] | Midbrain organoids | CRISPR/Cas9-mediated homozygous knockout of DNAJC6 in hESCs | mDAN degeneration, α-synuclein aggregation, increased neuronal firing frequencies, mitochondrial and lysosomal defects |
|
| Huntington’s disease (HD) | Conforti et al., 2018 [133] | Cerebral organoids | Patient iPSC-derived | Defective progenitor identity acquisition, abnormal neuronal specification, and disrupted cellular organization |
| Zhang et al., 2019 [134] | Cerebral organoids | Patient iPSC-derived and isogenic HD hESC-derived | Impaired cell cycle, disrupted neuroepithelial structures, and premature neurogenesis |
|
| Glioblastoma | Linkous et al., 2019 [139] | Cerebral organoid glioma (GLICO) | Patient-derived glioma stem cells cocultured with hESC-derived cerebral organoids | Rapid and deep invasion of glioblastoma cells into cerebral organoids; invasive tumor phenotypes in hybrid organoids |
| Jacob et al., 2020b [143] | Glioblastoma organoids | Patient-derived | Recapitulated histological, cellular, and transcriptomic features of glioblastoma; aggressive infiltration after transplantation |
|
