Table 1 Human neurodevelopmental diseases modeled using brain organoids
From: Modeling human neurodevelopmental diseases with brain organoids
Disease | Reference | Cell sources | Reprogramming or gene editing | Organoid types | Phenotypes | Relevant phenotypes in animal models |
|---|---|---|---|---|---|---|
MCPH | Zhang et al. 2019 | hESCs | CRISPR/Cas9-mediated WDR62 knockout | Cerebral organoids | Smaller organoids, premature differentiation of NPCs, reduction in oRGs proliferation | Mild effect on brain size, little change in neuroepithelium differentiation (Pulvers et al. 2010), reduced NPCs proliferation (Fish et al. 2006) |
Lancaster et al. 2013 | Patient fibroblasts | Lentivirus expressing OSKM | Cerebral organoids | Premature neural differentiation, smaller organoids | ||
Li et al. 2017a | Patient fibroblasts | Retrovirus expressing OSKM | Cortical organoids | Less organized neuroepithelium, fewer mature neurons, smaller organoids | ||
Esk et al. 2020 | hESCs | CRISPR/Cas9-mediated IER3IP1 knockout | Cerebral organoids | Smaller organoids, smaller neural rosettes | ||
ASD | Mariani et al. 2015 | Patient fibroblasts | Retrovirus expressing OSKM | Telencephalic organoids | Increased production of GABAergic lineage (progenitors and neurons) | Decreased GABAergic neurotransmission (Wang et al. 2021), disruption of cortico-striatal synapses (Peça et al. 2011) |
Schafer et al. 2019 | Patient fibroblasts | Retrovirus expressing OSKM | Forebrain organoids | Abnormal morphology of cortical neurons | ||
Wang et al. 2017 | Patient fibroblasts | CRISPR/Cas9-mediated CHD8 knockout | Cerebral organoids | Increased production of GABAergic interneurons | ||
RTT | Mellios et al. 2018 | Patient fibroblasts | Retrovirus expressing OSKM | Cerebral organoids | Dysregulation in miRNA expression and neurogenesis | Abnormal morphology of cortical neurons (Jugloff et al. 2005), alteration in interneuron subtypes (Tomassy et al. 2014) |
Xiang et al. 2020 | hESCs | TALEN- and CRISPR/Cas9-mediated MECP2 knockout and knockin | hMGEOs and hCOs | Abnormal morphology and function of GABAergic interneurons | ||
Gomes et al. 2020 | Patient fibroblasts | Retrovirus expressing OSKM | Dorsal forebrain organoids, ventral forebrain organoids, assembloids | Premature neurons with functional defect | ||
TS | Krey et al. 2013 | Patient fibroblasts | Modified mRNA cocktail of OSKM | Cerebral organoids | Aberrant dendrite retraction and dyregulation of RhoA signaling in cortical neurons | Disrupted neurite outgrowth and impaired migration of cortical neurons (Kamijo et al. 2018; Panagiotakos et al. 2019) |
Birey et al. 2017 | Patient fibroblasts | Retrovirus expressing OSKM | hCS, hSS, assembloids | Abnormal interneuron migration | ||
TSC | Blair et al. 2018 | hESCs | CRISPR/Cas9-mediated TSC1 and TSC2 knockout | Cortical organoids | Biased toward astroglial differentiation, activation of mTORC1 signaling | Increased astroglial differentiation (Uhlmann et al. 2002), decreased glutamate transport (Zeng et al. 2010) |
Dooves et al. 2021 | Patient fibroblasts | Lentivirus expressing OSKM | Cortical organoids | Increased gilogenesis, increased GABAergic synapses | ||
DS | Xu et al. 2019 | Patient fibroblasts | Sendai virus expressing OSKM | Forebrain organoids | Overproduction of GABAergic interneurons | Increased GABAergic neurotransmission (Kleschevnikov et al. 2012; MartÃnez-Cué et al. 2013), smaller brain volume (Belichenko et al. 2009) |
Tang et al. 2021 | Patient fibroblasts | Sendai virus expressing OSKM | Cerebral organoids | Smaller organoids, dysregulation of the DSCAM/PAK1 pathway |