参考文献
［1］Reubinoff B E，Itsykson P，Turetsky T，et al.Neural progenitors from human embryonic stem cells.Nat Biotechnol，2001，19（12）：1134-1140.
［2］Zhang S C，Wernig M，Duncan I D，et al.In vitro differentiation of transplantable neural precursors from human embryonic stem cells.Nat Biotechnol，2001，19（12）：1129-1133.
［3］Munoz-Sanjuan I，Brivanlou A H.Neural induction，the default model and embryonic stem cells.Nat Rev Neurosci，2002，3（4）：271-280.
［4］Eiraku M，Watanabe K，Matsuo-Takasaki M，et al.Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals.Cell Stem Cell，2008，3（5）：519-532.
［5］Lancaster M A，Renner M，Martin C A，et al.Cerebral organoids model human brain development and microcephaly.Nature，2013，501（7467）：373-379.
［6］Lancaster M A，Corsini N S，Wolfinger S，et al.Guided self-organization and cortical plate formation in human brain organoids.Nat Biotechnol，2017，35（7）：659-666.
［7］Kadoshima T，Sakaguchi H，Nakano T，et al.Self-organization of axial polarity，inside-out layer pattern，and species-specific progenitor dynamics in human ES cell-derived neocortex.Proc Natl Acad Sci U S A，2013，110（50）：20284-20289.
［8］Chambers S M，Fasano C A，Papapetrou E P，et al.Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling.Nat Biotechnol，2009，27（3）：275-280.
［9］Bagley J A，Reumann D，Bian S，et al.Fused cerebral organoids model interactions between brain regions.Nature Methods，2017，14（7）：743.
［10］Birey F，Andersen J，Makinson C D，et al.Assembly of functionally integrated human forebrain spheroids.Nature，2017，545（7652）：54-59.
［11］Xiang Y，Tanaka Y，Patterson B，et al.Fusion of Regionally specified hPSC-derived organoids models human brain development and interneuron migration.Cell Stem Cell，2017，21（3）：383-398.
［12］Mariani J，Coppola G，Zhang P，et al.FOXG1-dependent dysregulation of GABA/Glutamate neuron differentiation in autism spectrum disorders.Cell，2015，162（2）：375-390.
［13］Pasca A M，Sloan S A，Clarke L E，et al.Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.Nat Methods，2015，12（7）：671-678.
［14］Qian X Y，Nguyen H N，Song M M，et al.Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure.Cell，2016，165（5）：1238-1254.
［15］Pellegrini L，Bonfio C，Chadwick J，et al.Human CNS barrier-forming organoids with cerebrospinal fluid production.Science，2020，369（6500）.
［16］Miura Y，Li M Y，Birey F，et al.Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells.Nat Biotechnol，2020，38（12）：1421-1430.
［17］Xiang Y，Tanaka Y，Cakir B，et al.hESC-derived thalamic organoids form reciprocal projections when fused with cortical organoids.Cell Stem Cell.2019，24（3）：487-497.
［18］Huang W K，Wong S Z H，Pather S R，et al.Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.Cell Stem Cell，2021，28（9）：1657-1670.
［19］Jo J，Xiao Y，Sun A X，et al.Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons.Cell Stem Cell，2016，19（2）：248-257.
［20］Muguruma K，Nishiyama A，Kawakami H，et al.Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.Cell Rep，2015，10（4）：537-550.
［21］Birey F，Li M Y，Gordon A，et al.Dissecting the molecular basis of human interneuron migration in forebrain assembloids from Timothy syndrome.Cell Stem Cell，2022，29（2）：248-264.
［22］Pasca S P.Assembling human brain organoids.Science，2019，363（6423）：126-127.
［23］Mich J K，Close J L，Levi B P.Putting two heads together to build a better brain.Cell Stem Cell，2017，21（3）：289-290.
［24］Vogt N.Assembloids.Nat Methods，2021，18（1）：27.
［25］Giandomenico S L，Mierau S B，Gibbons G M，et al.Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output.Nature Neuroscience，2019，22（4）：669.
［26］Andersen J，Revah O，Miura Y，et al.Generation of functional human 3D cortico-motor assembloids.Cell，2020，183（7）：1913-1929.
［27］Shi Y，Sun L，Wang M，et al.Vascularized human cortical organoids（vOrganoids）model cortical development in vivo.PLoS Biol，2020，18（5）：e3000705.
［28］Pham M T，Pollock K M，Rose M D，et al.Generation of human vascularized brain organoids.Neuroreport，2018，29（7）：588-593.
［29］Wang L，Sievert D，Clark A E，et al.A human three-dimensional neural-perivascular“assembloid”promotes astrocytic development and enables modeling of SARS-Co V-2 neuropathology.Nature Medicine，2021，27（9）：1600.
［30］Cakir B，Xiang Y，Tanaka Y，et al.Engineering of human brain organoids with a functional vascular-like system.Nat Methods，2019，16（11）：1169-1175.
［31］Sun X Y，Ju X C，Li Y，et al.Generation of vascularized brain organoids to study neurovascular interactions.Elife，2022，11.
［32］Mansour A A，Goncalves J T，Bloyd C W，et al.An in vivo model of functional and vascularized human brain organoids.Nat Biotechnol，2018，36（5）：432-441.
［33］Jin M，Xu R，Wang L，et al.Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer's disease.Cell Stem Cell，2022，29（7）：1135-1153.
［34］Abud E M，Ramirez R N，Martinez E S，et al.iPSC-derived human microglia-like cells to study neurological diseases.Neuron，2017，94（2）：278-293.
［35］Cakir B，Tanaka Y，Kiral F R，et al.Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids.Nat Commun，2022，13（1）：430.
［36］Benito-Kwiecinski S，Giandomenico S L，Sutcliffe M，et al.An early cell shape transition drives evolutionary expansion of the human forebrain.Cell，2021，184（8）：2084-2102.
［37］Velasco S，Kedaigle A J，Simmons S K，et al.Individual brain organoids reproducibly form cell diversity of the human cerebral cortex.Nature，2019，570（7762）：523-527.
［38］Quadrato G，Nguyen T，Macosko E Z，et al.Cell diversity and network dynamics in photosensitive human brain organoids.Nature，2017，545（7652）：48-53.
［39］Fleck J S，Sanchis-Calleja F，He Z，et al.Resolving organoid brain region identities by mapping single-cell genomic data to reference atlases.Cell Stem Cell，2021，28（6）：1177-1180.
［40］Petilla Interneuron Nomenclature G，Ascoli G A，Alonso-Nanclares L，et al.Petilla terminology：nomenclature of features of GABAergic interneurons of the cerebral cortex.Nat Rev Neurosci，2008，9（7）：557-568.
［41］Bhaduri A，Andrews M G，Mancia Leon W，et al.Cell stress in cortical organoids impairs molecular subtype specification.Nature，2020，578（7793）：142-148.
［42］Marton R M，Miura Y，Sloan S A，et al.Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures.Nat Neurosci，2019，22（3）：484-491.
［43］Madhavan M，Nevin Z S，Shick H E，et al.Induction of myelinating oligodendrocytes in human cortical spheroids.Nat Methods，2018，15（9）：700-706.
［44］Trujillo C A，Gao R，Negraes P D，et al.Complex oscillatory waves emerging from cortical organoids model early human brain network development.Cell Stem Cell，2019，25（4）：558-569.
［45］Fischer J，Ortuno E F，Marsoner F，et al.Human-specific ARHGAP11B ensures human-like basal progenitor levels in hominid cerebral organoids.EMBO Rep，2022，23（11）：e54728.
［46］Ju X C，Hou Q Q，Sheng A L，et al.The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice.Elife，2016，5.
［47］Hou Q Q，Xiao Q，Sun X Y，et al.TBC1D3 promotes neural progenitor proliferation by suppressing the histone methyltransferase G9a.Sci Adv，2021，7（3）.
［48］Fiddes I T，Lodewijk G A，Mooring M，et al.Human-specific NOTCH2NL genes affect notch signaling and cortical neurogenesis.Cell，2018，173（6）：1356-1369.
［49］Suzuki I K，Gacquer D，Van Heurck R，et al.Human-specific NOTCH2NL genes expand cortical neurogenesis through Delta/Notch regulation.Cell，2018，173（6）：1370.
［50］Otani T，Marchetto M C，Gage F H，et al.2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size.Cell Stem Cell，2016，18（4）：467-480.
［51］Mora-Bermudez F，Badsha F，Kanton S，et al.Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development.Elife，2016，5.
［52］Wang L，Hou S，Han Y G.Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex.Nat Neurosci，2016，19（7）：888-896.
［53］Pollen A A，Bhaduri A，Andrews M G，et al.Establishing cerebral organoids as models of human-specific brain evolution.Cell，2019，176（4）：743.
［54］Pinson A，Xing L，Namba T，et al.Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals.Science，2022，377（6611）：1170.
［55］Kanton S，Boyle M J，He Z，et al.Organoid single-cell genomic atlas uncovers human-specific features of brain development.Nature，2019，574（7778）：418-422.
［56］Trujillo C A，Rice E S，Schaefer N K，et al.Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment.Science，2021，371（6530）.
［57］Gabriel E，Wason A，Ramani A，et al.CPAP promotes timely cilium disassembly to maintain neural progenitor pool.EMBO J，2016，35（8）：803-819.
［58］An H L，Kuo H C，Tang T K.Modeling human primary microcephaly with hiPSC-derived brain organoids carrying CPAP-E1235V disease-associated mutant protein.Front Cell Dev Biol，2022，10：830432.
［59］Li R，Sun L，Fang A，et al.Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like（ASPM related primary）microcephaly disease.Protein Cell，2017，8（11）：823-833.
［60］Omer Javed A，Li Y，Muffat J，et al.Microcephaly modeling of kinetochore mutation reveals a brain-specific phenotype.Cell Rep，2018，25（2）：368-382.
［61］Coulter M E，Dorobantu C M，Lodewijk G A，et al.The ESCRT-III protein CHMP1A mediates secretion of sonic hedgehog on a distinctive subtype of extracellular vesicles.Cell Rep，2018，24（4）：973-986.
［62］Bendriem R M，Singh S，Aleem A A，et al.Tight junction protein occludin regulates progenitor Self-Renewal and survival in developing cortex.Elife，2019，8.
［63］Zhang W，Yang S L，Yang M，et al.Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors.Nat Commun，2019，10（1）：2612.
［64］Wang L，Li Z，Sievert D，et al.Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly.Nat Commun，2020，11（1）：4038.
［65］Bowers M，Liang T，Gonzalez-Bohorquez D，et al.FASN-dependent lipid metabolism links neurogenic stem/progenitor cell activity to learning and memory deficits.Cell Stem Cell，2020，27（1）：98-109.
［66］Gonzalez-Bohorquez D，Gallego Lopez I M，Jaeger B N，et al.FASN-dependent de novo lipogenesis is required for brain development.Proc Natl Acad Sci U S A，2022，119（2）.
［67］Hu M，Li H，Huang Z，et al.Novel compound heterozygous mutation in STAMBP causes a neurodevelopmental disorder by disrupting cortical proliferation.Front Neurosci，2022，16：963813.
［68］Lin V J T，Hu J，Zolekar A，et al.Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.Cell Death Dis，2022，13（3）：262.
［69］Fair S R，Schwind W，Julian D L，et al.Cerebral organoids containing an AUTS2 missense variant model microcephaly.Brain，2023，146（1）：387-404.
［70］Dhaliwal N，Choi W W Y，Muffat J，et al.Modeling PTEN overexpression-induced microcephaly in human brain organoids.Mol Brain，2021，14（1）：131.
［71］Urresti J，Zhang P，Moran-Losada P，et al.Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism.Mol Psychiatry，2021，26（12）：7560-7580.
［72］Esk C，Lindenhofer D，Haendeler S，et al.A human tissue screen identifies a regulator of ER secretion as a brain-size determinant.Science，2020，370（6519）：935.
［73］Li Y，Muffat J，Omer A，et al.Induction of expansion and folding in human cerebral organoids.Cell Stem Cell，2017，20（3）：385-396.
［74］Zhang W，Ma L，Yang M，et al.Cerebral organoid and mouse models reveal a RAB39b-PI3Km TOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes.Genes Dev，2020，34（7-8）：580-597.
［75］Villa C E，Cheroni C，Dotter C P，et al.CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories.Cell Rep，2022，39（1）：110615.
［76］Dang L T，Vaid S，Lin G，et al.STRADA-mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation.Dev Neurobiol，2021，81（5）：696-709.
［77］Suzuki I K，Gacquer D，Van Heurck R，et al.Human-specific NOTCH2NL genes expand cortical neurogenesis through Delta/Notch regulation.Cell，2018，173（6）：1370-1384.
［78］Bershteyn M，Nowakowski T J，Pollen A A，et al.Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia.Cell Stem Cell，2017，20（4）：435-449.
［79］Iefremova V，Manikakis G，Krefft O，et al.An organoid-based model of cortical development identifies non-cell-autonomous defects in wnt signaling contributing to miller-dieker syndrome.Cell Rep，2017，19（1）：50-59.
［80］Klaus J，Kanton S，Kyrousi C，et al.Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia.Nat Med，2019，25（4）：561-568.
［81］Buchsbaum I Y，Kielkowski P，Giorgio G，et al.ECE2 regulates neurogenesis and neuronal migration during human cortical development.EMBO Rep，2020，21（5）：e48204.
［82］O'neill A C，Kyrousi C，Klaus J，et al.A primate-specific isoform of PLEKHG6 regulates neurogenesis and neuronal migration.Cell Rep，2018，25（10）：2729-2741.
［83］Tang X Y，Xu L，Wang J，et al.DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome.J Clin Invest，2021，131（12）.
［84］Xu R，Brawner A T，Li S，et al.OLIG2 drives abnormal neurodevelopmental phenotypes in human iPSC-based organoid and chimeric mouse models of down syndrome.Cell Stem Cell，2019，24（6）：908-926.
［85］Alic I，Goh P A，Murray A，et al.Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.Mol Psychiatry，2021，26（10）：5766-5788.
［86］Trujillo C A，Adams J W，Negraes P D，et al.Pharmacological reversal of synaptic and network pathology in human MECP2-KO neurons and cortical organoids.EMBO Mol Med，2021，13（1）：e12523.
［87］Mellios N，Feldman D A，Sheridan S D，et al.MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling.Mol Psychiatry，2018，23（4）：1051-1065.
［88］Samarasinghe R A，Miranda O A，Buth J E，et al.Identification of neural oscillations and epileptiform changes in human brain organoids.Nat Neurosci，2021，24（10）：1488-1500.
［89］Xiang Y，Tanaka Y，Patterson B，et al.Dysregulation of BRD4 function underlies the functional abnormalities of MeCP2 mutant neurons.Mol Cell，2020，79（1）：84-98.
［90］Gomes A R，Fernandes T G，Vaz S H，et al.Modeling rett syndrome with human patientspecific forebrain organoids.Front Cell Dev Biol，2020，8：610427.
［91］Raj N，Mceachin Z T，Harousseau W，et al.Cell-type-specific profiling of human cellular models of fragile X syndrome reveal PI3K-dependent defects in translation and neurogenesis.Cell Rep，2021，35（2）：108991.
［92］Kang Y，Zhou Y，Li Y，et al.A human forebrain organoid model of fragile X syndrome exhibits altered neurogenesis and highlights new treatment strategies.Nat Neurosci，2021，24（10）：1377-1391.
［93］Brighi C，Salaris F，Soloperto A，et al.Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs.Cell Death Dis，2021，12（5）：498.
［94］Sun A X，Yuan Q，Fukuda M，et al.Potassium channel dysfunction in human neuronal models of Angelman syndrome.Science，2019，366（6472）：1486-1492.
［95］Sen D，Voulgaropoulos A，Drobna Z，et al.Human cerebral organoids reveal early spatiotemporal dynamics and pharmacological responses of UBE3A.Stem Cell Reports，2020，15（4）：845-854.
［96］Revah O，Gore F，Kelley K W，et al.Maturation and circuit integration of transplanted human cortical organoids.Nature，2022，610（7931）：319-326.(https://www.daowen.com)
［97］Meikle L，Talos D M，Onda H，et al.A mouse model of tuberous sclerosis：neuronal loss of Tsc1 causes dysplastic and ectopic neurons，reduced myelination，seizure activity，and limited survival.J Neurosci，2007，27（21）：5546-5558.
［98］Blair J D，Hockemeyer D，Bateup H S.Genetically engineered human cortical spheroid models of tuberous sclerosis.Nat Med，2018，24（10）：1568-1578.
［99］Dooves S，Van Velthoven A J H，Suciati L G，et al.Neuron-glia interactions in tuberous sclerosis complex affect the synaptic balance in 2D and organoid cultures.Cells，2021，10（1）.
［100］Eichmuller O L，Corsini N S，Vertesy A，et al.Amplification of human interneuron progenitors promotes brain tumors and neurological defects.Science，2022，375（6579）：eabf5546.
［101］Steinberg D J，Repudi S，Saleem A，et al.Modeling genetic epileptic encephalopathies using brain organoids.EMBO Mol Med，2021，13（8）：e13610.
［102］Repudi S，Steinberg D J，Elazar N，et al.Neuronal deletion of Wwox，associated with WOREE syndrome，causes epilepsy and myelin defects.Brain，2021，144（10）：3061-3077.
［103］Wu W，Yao H，Negraes P D，et al.Neuronal hyperexcitability and ion channel dysfunction in CDKL5-deficiency patient iPSC-derived cortical organoids.Neurobiol Dis，2022，174：105882.
［104］Di Matteo F，Pipicelli F，Kyrousi C，et al.Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy.EMBO Mol Med，2020，12（6）：e11419.
［105］Kirihara T，Luo Z，Chow S Y A，et al.A human induced pluripotent stem cell-derived tissue model of a cerebral tract connecting two cortical regions.iScience，2019，14：301-311.
［106］Khan T A，Revah O，Gordon A，et al.Neuronal defects in a human cellular model of 22q11.2 deletion syndrome.Nat Med，2020，26（12）：1888-1898.
［107］Johnstone M，Vasistha N A，Barbu M C，et al.Reversal of proliferation deficits caused by chromosome 16p13.11 microduplication through targeting NFkappaB signaling：an integrated study of patient-derived neuronal precursor cells，cerebral organoids and in vivo brain imaging.Mol Psychiatry，2019，24（2）：294-311.
［108］Nour M M，Howes O D.Interpreting the neurodevelopmental hypothesis of schizophrenia in the context of normal brain development and ageing.Proc Natl Acad Sci U S A，2015，112（21）：E2745.
［109］Paulsen B，Velasco S，Kedaigle A J，et al.Autism genes converge on asynchronous development of shared neuron classes.Nature，2022，602（7896）：268-273.
［110］Srikanth P，Lagomarsino V N，Muratore C R，et al.Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids.Transl Psychiatry，2018，8（1）：77.
［111］Sawada T，Chater T E，Sasagawa Y，et al.Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids.Mol Psychiatry，2020，25（11）：2695-2711.
［112］Qian X，Su Y，Adam C D，et al.Sliced human cortical organoids for modeling distinct cortical layer formation.Cell Stem Cell，2020，26（5）：766-781.
［113］Ye F，Kang E，Yu C，et al.DISC1 regulates neurogenesis via modulating kinetochore attachment of Ndel1/Nde1 during mitosis.Neuron，2017，96（5）：1041-1054.
［114］Benson C A，Powell H R，Liput M，et al.Immune factor，TNfalpha，disrupts human brain organoid development similar to schizophrenia-schizophrenia increases developmental vulnerability to TNFalpha.Front Cell Neurosci，2020，14：233.
［115］Na K S，Jung H Y，Kim Y K.The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry，2014，48：277-286.
［116］Kathuria A，Lopez-Lengowski K，Jagtap S S，et al.Transcriptomic landscape and functional characterization of induced pluripotent stem cell-derived cerebral organoids in schizophrenia.JAMA Psychiatry，2020，77（7）：745-754.
［117］Kathuria A，Lopez-Lengowski K，Vater M，et al.Transcriptome analysis and functional characterization of cerebral organoids in bipolar disorder.Genome Med，2020，12（1）：34.
［118］Osete J R，Akkouh I A，Ievglevskyi O，et al.Transcriptional and functional effects of lithium in bipolar disorder iPSC-derived cortical spheroids.Mol Psychiatry，2023.
［119］Le Grand J N，Gonzalez-Cano L，Pavlou M A，et al.Neural stem cells in Parkinson's disease：a role for neurogenesis defects in onset and progression.Cell Mol Life Sci，2015，72（4）：773-797.
［120］Schwamborn J C.Is Parkinson's disease a neurodevelopmental disorder and will brain organoids help us to understand it？Stem Cells Dev，2018，27（14）：968-975.
［121］Choi S H，Kim Y H，Hebisch M，et al.A three-dimensional human neural cell culture model of Alzheimer's disease.Nature，2014，515（7526）：274-278.
［122］Gonzalez C，Armijo E，Bravo-Alegria J，et al.Modeling amyloid beta and tau pathology in human cerebral organoids.Mol Psychiatry，2018，23（12）：2363-2674.
［123］Zhao J，Fu Y，Yamazaki Y，et al.APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids.Nat Commun，2020，11（1）：5540.
［124］Lin Y T，Seo J，Gao F，et al.APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC-derived brain cell types.Neuron，2018，98（6）：1141-1154.
［125］Blanchard J W，Akay L A，Davila-Velderrain J，et al.APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.Nature，2022，611（7937）：769-779.
［126］Choi H，Kim H J，Yang J，et al.Acetylation changes tau interactome to degrade tau in Alzheimer's disease animal and organoid models.Aging Cell，2020，19（1）：e13081.
［127］Smits L M，Reinhardt L，Reinhardt P，et al.Modeling Parkinson's disease in midbrain-like organoids.NPJ Parkinsons Dis，2019，5：5.
［128］Kim H，Park H J，Choi H，et al.Modeling G2019S-LRRK2 sporadic Parkinson's disease in 3D midbrain organoids.Stem Cell Reports，2019，12（3）：518-531.
［129］Zagare A，Barmpa K，Smajic S，et al.Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-p.Gly2019Ser-associated gene expression.Am J Hum Genet，2022，109（2）：311-327.
［130］Walter J，Bolognin S，Poovathingal S K，et al.The Parkinson's-disease-associated mutation LRRK2-G2019S alters dopaminergic differentiation dynamics via NR2F1.Cell Rep，2021，37（3）：109864.
［131］Wulansari N，Darsono W H W，Woo H J，et al.Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson's disease-linked DNAJC6 mutations.Sci Adv，2021，7（8）.
［132］Jarazo J，Barmpa K，Modamio J，et al.Parkinson's disease phenotypes in patient neuronal cultures and brain organoids improved by 2-hydroxypropyl-beta-cyclodextrin treatment.Mov Disord，2022，37（1）：80-94.
［133］Saudou F，Humbert S.The biology of huntingtin.Neuron，2016，89（5）：910-926.
［134］Conforti P，Besusso D，Bocchi V D，et al.Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes.Proc Natl Acad Sci U S A，2018，115（4）：E762-E71.
［135］Liu C，Fu Z，Wu S，et al.Mitochondrial HSF1 triggers mitochondrial dysfunction and neurodegeneration in Huntington's disease.EMBO Mol Med，2022，14（7）：e15851.
［136］Szebenyi K，Wenger L M D，Sun Y，et al.Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology.Nat Neurosci，2021，24（11）：1542-1554.
［137］Meijboom K E，Abdallah A，Fordham N P，et al.CRISPR/Cas9-mediated excision of ALS/FTD-causing hexanucleotide repeat expansion in C9ORF72 rescues major disease mechanisms in vivo and in vitro.Nat Commun，2022，13（1）：6286.
［138］Ho W Y，Chang J C，Lim K，et al.TDP-43 mediates SREBF2-regulated gene expression required for oligodendrocyte myelination.J Cell Biol，2021，220（9）.
［139］Zou H，Wang J Y，Ma G M，et al.The function of FUS in neurodevelopment revealed by the brain and spinal cord organoids.Mol Cell Neurosci，2022，123：103771.
［140］Bley A E，Giannikopoulos O A，Hayden D，et al.Natural history of infantile G（M2）gangliosidosis.Pediatrics，2011，128（5）：e1233-1241.
［141］Allende M L，Cook E K，Larman B C，et al.Cerebral organoids derived from Sandhoff diseaseinduced pluripotent stem cells exhibit impaired neurodifferentiation.J Lipid Res，2018，59（3）：550-563.
［142］Inak G，Rybak-Wolf A，Lisowski P，et al.Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome.Nat Commun，2021，12（1）：1929.
［143］Hubert C G，Rivera M，Spangler L C，et al.A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo.Cancer Res，2016，76（8）：2465-2477.
［144］Jacob F，Salinas R D，Zhang D Y，et al.A patient-derived glioblastoma organoid model and biobank recapitulates inter-and intra-tumoral heterogeneity.Cell，2020，180（1）：188-204.
［145］Jacob F，Ming G L，Song H.Generation and biobanking of patient-derived glioblastoma organoids and their application in CAR T cell testing.Nat Protoc，2020，15（12）：4000-4033.
［146］Linkous A，Balamatsias D，Snuderl M，et al.Modeling patient-derived glioblastoma with cerebral organoids.Cell Rep，2019，26（12）：3203-3211.
［147］Bian S，Repic M，Guo Z，et al.Genetically engineered cerebral organoids model brain tumor formation.Nat Methods，2018，15（8）：631-639.
［148］Ogawa J，Pao G M，Shokhirev M N，et al.Glioblastoma model using human cerebral organoids.Cell Rep，2018，23（4）：1220-1229.
［149］Northcott P A，Buchhalter I，Morrissy A S，et al.The whole-genome landscape of medulloblastoma subtypes.Nature，2017，547（7663）：311-317.
［150］Ballabio C，Anderle M，Gianesello M，et al.Modeling medulloblastoma in vivo and with human cerebellar organoids.Nat Commun，2020，11（1）：583.
［151］Valencia A M，Collings C K，Dao H T，et al.Recurrent SMARCB1 mutations reveal a nucleosome acidic patch interaction site that potentiates mSWI/SNF complex chromatin remodeling.Cell，2019，179（6）：1342-1356.
［152］Parisian A D，Koga T，Miki S，et al.SMARCB1 loss interacts with neuronal differentiation state to block maturation and impact cell stability.Genes Dev，2020，34（19-20）：1316-1329.
［153］Zhu Z，Mesci P，Bernatchez J A，et al.Zika virus targets glioblastoma stem cells through a SOX2-Integrin alpha（v）beta（5）axis.Cell Stem Cell，2020，26（2）：187-204.
［154］Garcez P P，Loiola E C，Madeiro Da Costa R，et al.Zika virus impairs growth in human neurospheres and brain organoids.Science，2016，352（6287）：816-818.
［155］Cugola F R，Fernandes I R，Russo F B，et al.The Brazilian Zika virus strain causes birth defects in experimental models.Nature，2016，534（7606）：267-271.
［156］Qian X，Nguyen H N，Song M M，et al.Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure.Cell，2016，165（5）：1238-1254.
［157］Krenn V，Bosone C，Burkard T R，et al.Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly.Cell Stem Cell，2021，28（8）：1362-1379.
［158］D'aiuto L，Bloom D C，Naciri J N，et al.Modeling herpes simplex virus 1 infections in human central nervous system neuronal cells using two-and three-dimensional cultures derived from induced pluripotent stem cells.J Virol，2019，93（9）.
［159］Sun G，Chiuppesi F，Chen X，et al.Modeling human cytomegalovirus-induced microcephaly in human iPSC-derived brain organoids.Cell Rep Med，2020，1（1）：100002.
［160］Brown R M，Rana P，Jaeger H K，et al.Human cytomegalovirus compromises development of cerebral organoids.J Virol，2019，93（17）.
［161］Sison S L，O'brien B S，Johnson A J，et al.Human cytomegalovirus disruption of calcium signaling in neural progenitor cells and organoids.J Virol，2019，93（17）.
［162］Xu Y P，Qiu Y，Zhang B，et al.Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids.Cell Res，2019，29（4）：265-273.
［163］Dang J，Tiwari S K，Lichinchi G，et al.Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3.Cell Stem Cell，2016，19（2）：258-265.
［164］Ramani A，Muller L，Ostermann P N，et al.SARS-Co V-2 targets neurons of 3D human brain organoids.EMBO J，2020，39（20）：e106230.
［165］Tiwari S K，Wang S，Smith D，et al.Revealing tissue-specific SARS-Co V-2 infection and host responses using human stem cell-derived lung and cerebral organoids.Stem Cell Reports，2021，16（3）：437-445.
［166］Mcmahon C L，Staples H，Gazi M，et al.SARS-Co V-2 targets glial cells in human cortical organoids.Stem Cell Reports，2021，16（5）：1156-1164.
［167］Jacob F，Pather S R，Huang W K，et al.Human pluripotent stem cell-derived neural cells and brain organoids reveal SARS-Co V-2 neurotropism predominates in choroid plexus epithelium.Cell Stem Cell，2020，27（6）：937-950.
［168］Pellegrini L，Albecka A，Mallery D L，et al.SARS-Co V-2 infects the brain choroid plexus and disrupts the blood-CSF barrier in human brain organoids.Cell Stem Cell，2020，27（6）：951-961.
［169］Wang L，Sievert D，Clark A E，et al.A human three-dimensional neural-perivascular“assembloid”promotes astrocytic development and enables modeling of SARS-Co V-2 neuropathology.Nat Med，2021，27（9）：1600-1606.
［170］Seo H H，Han H W，Lee S E，et al.Modelling Toxoplasma gondii infection in human cerebral organoids.Emerg Microbes Infect，2020，9（1）：1943-1954.
［171］Groveman B R，Foliaki S T，Orru C D，et al.Sporadic Creutzfeldt-Jakob disease prion infection of human cerebral organoids.Acta Neuropathol Commun，2019，7（1）：90.
［172］Groveman B R，Ferreira N C，Foliaki S T，et al.Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease.Scientific reports，2021，11（1）：5165.
［173］Kim J，Koo B K，Knoblich J A.Human organoids：model systems for human biology and medicine.Nat Rev Mol Cell Biol，2020，21（10）：571-584.
［174］Gordon P H，Meininger V.How can we improve clinical trials in amyotrophic lateral sclerosis？Nat Rev Neurol，2011，7（11）：650-654.
［175］Xu G，Ran Y，Fromholt S E，et al.Murine Abeta over-production produces diffuse and compact Alzheimer-type amyloid deposits.Acta Neuropathol Commun，2015，3：72.
［176］Sinha G.The organoid architect.Science，2017，357（6353）：746-749.
［177］Zhou T，Tan L，Cederquist G Y，et al.High-content screening in hPSC-neural progenitors identifies drug candidates that inhibit Zika virus infection in fetal-like organoids and adult brain.Cell Stem Cell，2017，21（2）：274-283.
［178］Zhu Y，Wang L，Yin F，et al.Probing impaired neurogenesis in human brain organoids exposed to alcohol.Integr Biol（Camb），2017，9（12）：968-978.
［179］Arzua T，Yan Y，Jiang C，et al.Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids.Transl Psychiatry，2020，10（1）：347.
［180］Donadoni M，Cicalese S，Sarkar D K，et al.Alcohol exposure alters pre-m RNA splicing of antiapoptotic Mcl-1L isoform and induces apoptosis in neural progenitors and immature neurons.Cell Death Dis，2019，10（6）：447.
［181］Wang Y，Wang L，Zhu Y，et al.Human brain organoid-on-a-chip to model prenatal nicotine exposure.Lab Chip，2018，18（6）：851-860.
［182］Lee C T，Chen J，Kindberg A A，et al.CYP3A5 mediates effects of cocaine on human neocorticogenesis：Studies using an in vitro 3D self-organized HPSC model with a single cortexlike unit.Neuropsychopharmacology，2017，42（3）：774-784.
［183］Dang J，Tiwari S K，Agrawal K，et al.Glial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids.Mol Psychiatry，2021，26（4）：1194-1207.
［184］Jiang M，Tang T，Liang X，et al.Maternal sevoflurane exposure induces temporary defects in interkinetic nuclear migration of radial glial progenitors in the fetal cerebral cortex through the Notch signalling pathway.Cell Prolif，2021，54（6）：e13042.
［185］Huang Y，Dai Y，Li M，et al.Exposure to cadmium induces neuroinflammation and impairs ciliogenesis in hESC-derived 3D cerebral organoids.Sci Total Environ，2021，797：149043.
［186］Wu Z，Lin D，Li Y.Pushing the frontiers：tools for monitoring neurotransmitters and neuromodulators.Nat Rev Neurosci，2022，23（5）：257-274.
［187］Zhang Z，Cheng X，Zhao Y，et al.Lighting up live-cell and in vivo central carbon metabolism with genetically encoded fluorescent sensors.Annu Rev Anal Chem（Palo Alto Calif），2020，13（1）：293-314.
［188］Thomson J A，Itskovitz-Eldor J，Shapiro S S，et al.Embryonic stem cell lines derived from human blastocysts.Science，1998，282（5391）：1145-1147.
［189］Takahashi K，Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell，2006，126（4）：663-676.
［190］Mandai M，Watanabe A，Kurimoto Y，et al.Autologous induced stem-cell-derived retinal cells for macular degeneration.N Engl J Med，2017，376（11）：1038-1046.
［191］Schweitzer J S，Song B，Herrington T M，et al.Personalized iPSC-derived dopamine progenitor cells for Parkinson's disease.N Engl J Med，2020，382（20）：1926-1932.
［192］Dong X，Xu S B，Chen X，et al.Human cerebral organoids establish subcortical projections in the mouse brain after transplantation.Mol Psychiatry，2021，26（7）：2964-2976.