Table 2.
Neurological disease modeling using brain organoids.
| Disease/Disorder | Mutation | Organoid model | Reference(s) | |
|---|---|---|---|---|
| Neurodevelopmental | ||||
| Macrocephaly | PTEN KO iPSCs | Cerebral organoids | Li, Muffat, et al. (2017) | |
| Microcephaly | Mutant ASPM patient iPSCs | Cortex-like organoids | Li, Sun, et al. (2017) | |
| WRD62 KO and mutant CDK5RAP2 patient iPSCs | Cerebral organoids | Lancaster et al. (2013) | ||
| Mutant CPAP patient iPSCs | Cerebral organoids | Gabriel et al. (2016) | ||
| Lissencephaly | Miller-Dieker syndrome patient iPSCs | Cerebral and forebrain organoids | Bershteyn et al. (2017) and Iefremova et al. (2017) | |
| LIS1 heterozygous KO ESCs | Brain organoids | Karzbrun, Kshirsagar, Cohen, Hanna, and Reiner (2018) | ||
| Neuronal heterotopia | PLEKHG6 OE and knockdown iPSCs | Cerebral organoids | O’Neill et al. (2018) | |
| Mutant DCHS1 and FAT4 patient iPSCs | Cerebral organoids | Klaus et al. (2019) | ||
| Rett Syndrome | MECP2 mutant patient iPSCs | Cerebral organoids | Mellios et al. (2018) | |
| Sandhoff disease | HEXB mutant patient iPSCs | Cerebral organoids | Allende et al. (2018) | |
| Angelman syndrome | UBE3A KO and AS patient iPSCs | Cortical spheroids | Sun et al. (2019) | |
| Leber congenital amaurosis | CEP290 mutant patient iPSCs | Retinal organoids | Parfitt et al. (2016) | |
| Hypoxia | Control ESCs and iPSCs | Cerebral and brain organoids and cortical spheroids | Boisvert, Means, Michaud, Madri, and Katz (2019), Daviaud, Chevalier, Friedel, and Zou (2019) and Paşca et al. (2019) | |
| Neuropsychiatric | ||||
| Autism | Idiopathic autism patient iPSCs | Cerebral organoids | Mariani et al. (2015) | |
| Heterozygous CHD8 KO iPSCs | Cerebral organoids | Wang et al. (2017) | ||
| Timothy syndrome patient iPSCs | Subcortical spheroids | Birey et al. (2017) | ||
| Schizophrenia | Mutant DISC1 patient iPSCs | Forebrain and sliced cortical organoids | Qian et al. (2020) and Ye et al. (2017) | |
| Mutant DISC1 iPSCs | Cerebral organoids | Srikanth et al. (2018) | ||
| 16p13.11 microduplication patient iPSCs | Cerebral organoids | Johnstone et al. (2018) | ||
| Schizophrenia patient iPSCs | Cerebral organoids | Stachowiak et al. (2017) | ||
| Neurodegenerative | ||||
| Alzheimer’s disease | Mutated APP or PSEN1 AD patient iPSCs | Brain organoids | Raja et al. (2016) | |
| Frontotemporal dementia | Mutated Tau P301L FTD patient iPSCs | Cerebral organoids | Seo et al. (2017) | |
| Parkinson’s disease | Mutant LRRK2 PD patient iPSCs | Midbrain organoids | Smits et al. (2019) | |
| Mutant LRRK2 iPSCs | Midbrain organoids | Kim, Park, et al. (2019) | ||
| Huntington’s disease | Expanded CAG repeat iPSCs | Cortical organoids | Conforti et al. (2018) | |
| Retinitis pigmentosa | RP patient iPSCs | Retinal organoids | Deng et al. (2018) | |
| Infectious | ||||
| Zika virus | Control iPSCs | Cerebral and forebrain organoids | Cugola et al. (2016), Garcez et al. (2016), and Qian et al. (2016) | |
| Herpes simplex virus | Control iPSCs | Brain organoids | D’Aiuto et al. (2019) | |
| Cytomegalovirus | Control iPSCs | Brain and cortical organoids | Sison et al. (2019) and Sun et al. (2020) | |
| Japanese encephalitis virus | Control iPSCs | Cortical organoids | Zhang et al. (2018) | |
| SARS-CoV-2 | Control iPSCs | Cerebral, cortical, hippocampus, hypothalamus, midbrain, and/or choroid plexus organoids | Jacob, Pather, et al. (2020), Pellegrini, Albecka, et al. (2020), Ramani et al. (2020), and Song et al. (2020) | |
| Chemical exposure | ||||
| Bisphenol A | Control iPSCs | Forebrain organoids | Qian et al. (2016) | |
| Ethanol | Control iPSCs | Brain and cerebral organoids | Arzua et al. (2020) and Zhu et al. (2017) | |
| Cocaine | Control iPSCs | Neocortical organoids | Lee et al. (2017) | |
| 5-MeO-DMT | Control iPSCs | Cerebral organoids | Dakic et al. (2017) | |
| Nicotine | Control iPSCs | Brain organoid-on-a-chip | Wang et al. (2018) | |
| Cannabinoid | Control iPSCs | Microfluidic assembled cerebral organoids | Ao et al. (2020) | |
| Neoplastic | ||||
| Tuberous Sclerosis | TSC1 and TSC2 KO iPSCs | Cortical spheroids | Blair et al. (2018) | |
| Glioma | HRAS OE and TP53 KO | Cerebral organoids | Ogawa et al. (2018) | |
| MYC, EGFR, and EGFRvIII OE; CDKN2A/B, NF1, PTEN, and TP53 KO | Cerebral organoids | Bian et al. (2018) | ||
| Control iPSCs and GSCs | Cerebral organoids | Linkous et al. (2019) | ||
| Control iPSCs and GSCs | Cerebral organoids | Krieger et al. (2020) | ||
| Medulloblastoma | Control iPSCs | Cerebellar organoids | Ballabio et al. (2020) | |
Summary of neurodevelopmental and neuropsychiatric disorders, neurodegenerative and infectious diseases, chemical exposures, and neoplasms modeled using brain organoids. Selected references are provided for further reading. KO, knock-out; OE, over-expression.