2025
Molecular hallmarks of hydrocephalus
Hale A, Zhou B, Rajan A, Duy P, Goolam M, Alper S, Lehtinen M, Lancaster M, Fame R, Kahle K. Molecular hallmarks of hydrocephalus. Science Translational Medicine 2025, 17: eadq1810. PMID: 40465691, DOI: 10.1126/scitranslmed.adq1810.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidBrain-CSF interfacePluripotent stem cell-derived cerebral organoidsStem cell dysfunctionAssociated with dilatationDisrupts synaptogenesisNeural stem cell dysfunctionMolecular classificationPharmacological treatmentCell dysfunctionImpaired neurogenesisBiomechanical instabilityHC subtypesGenome-widePleiotropic mechanismsCSF dynamicsNeural circuitryHydrocephalusEnvironmental insultsCerebral organoidsNeurodevelopmental comorbidities
2024
Dysregulation of miRNA expression and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids
Trudler D, Ghatak S, Bula M, Parker J, Talantova M, Luevanos M, Labra S, Grabauskas T, Noveral S, Teranaka M, Schahrer E, Dolatabadi N, Bakker C, Lopez K, Sultan A, Patel P, Chan A, Choi Y, Kawaguchi R, Stankiewicz P, Garcia-Bassets I, Kozbial P, Rosenfeld M, Nakanishi N, Geschwind D, Chan S, Lin W, Schork N, Ambasudhan R, Lipton S. Dysregulation of miRNA expression and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids. Molecular Psychiatry 2024, 30: 1479-1496. PMID: 39349966, PMCID: PMC11919750, DOI: 10.1038/s41380-024-02761-9.Peer-Reviewed Original ResearchMEF2C haploinsufficiency syndromeLoss-of-function mutationsCerebral organoidsHaploinsufficiency syndromeReceptor antagonistHiPSC-neuronsDecreased neurogenesisSevere formCerebrocortical neuronsAnimal studiesExtrasynaptic activationMEF2CAbnormal phenotypesNeurodevelopmentNeuronsDeficitsOrganoidsTranscription factorsMutationsNitroSynapsinGene networksDysregulation of miRNA expressionMassively parallel characterization of regulatory elements in the developing human cortex
Deng C, Whalen S, Steyert M, Ziffra R, Przytycki P, Inoue F, Pereira D, Capauto D, Norton S, Vaccarino F, Pollen A, Nowakowski T, Ahituv N, Pollard K, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Bendl J, Berretta S, Bharadwaj R, Bhattacharya A, Bicks L, Brennand K, Capauto D, Champagne F, Chatterjee T, Chatzinakos C, Chen Y, Chen H, Cheng Y, Cheng L, Chess A, Chien J, Chu Z, Clarke D, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Fullard J, Galani K, Galeev T, Gandal M, Gaynor S, Gerstein M, Geschwind D, Girdhar K, Goes F, Greenleaf W, Grundman J, Guo H, Guo Q, Gupta C, Hadas Y, Hallmayer J, Han X, Haroutunian V, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, Hoffman G, Huang Y, Huuki-Myers L, Hwang A, Hyde T, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kellis M, Khullar S, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Lee C, Lee D, Li J, Li M, Lin X, Liu S, Liu J, Liu J, Liu C, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Margolis M, Mariani J, Martinowich K, Maynard K, Mazariegos S, Meng R, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Moore J, Moran J, Mukamel E, Nairn A, Nemeroff C, Ni P, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollard K, Pollen A, Pratt H, Przytycki P, Purmann C, Qin Z, Qu P, Quintero D, Raj T, Rajagopalan A, Reach S, Reimonn T, Ressler K, Ross D, Roussos P, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Sestan N, Seyfried N, Shao Z, Shedd N, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Weinberger D, Wen C, Weng Z, Whalen S, White K, Willsey A, Won H, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Xu S, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Massively parallel characterization of regulatory elements in the developing human cortex. Science 2024, 384: eadh0559. PMID: 38781390, PMCID: PMC12085231, DOI: 10.1126/science.adh0559.Peer-Reviewed Original ResearchConceptsGene regulatory elementsRegulatory elementsRegulation of enhancer activityCharacterization of regulatory elementsCis-regulatory activityNeuronal developmentPrimary cellsEnhanced activityGene regulationHuman neuronal developmentNucleotide changesEnhancer sequencesSequence basisUpstream regulatorComprehensive catalogHuman cellsDeveloping cortexSequenceVariantsOrganoidsCellsCerebral organoidsCortexHuman cortexNucleotideMicroglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids
Wu J, Zhang J, Chen X, Wettschurack K, Que Z, Deming B, Olivero-Acosta M, Cui N, Eaton M, Zhao Y, Li S, Suzuki M, Chen I, Xiao T, Halurkar M, Mandal P, Yuan C, Xu R, Koss W, Du D, Chen F, Wu L, Yang Y. Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids. Molecular Psychiatry 2024, 29: 2424-2437. PMID: 38499656, DOI: 10.1038/s41380-024-02518-4.Peer-Reviewed Original ResearchAutism spectrum disorderSpine densityAssociated with autism spectrum disorderLower spine densitySynaptic transmissionHuman cellsPost-synapseProtein-truncating mutationsNeurodevelopmental disorder affecting 1Phagocytosis of synapsesNeuro-immune responsesImpaired learningIntellectual disabilityNeuro-immune interactionsHuman genetic studiesRestoring synaptic transmissionReduced synaptic transmissionAblation of microgliaSpectrum disorderResident immune cellsHuman cerebral organoid modelCerebral organoidsBrain developmentCerebral organoid modelSCN2A mutations
2023
Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors
Dell'Amico C, Salavarria M, Takeo Y, Saotome I, Dell'Anno M, Galimberti M, Pellegrino E, Cattaneo E, Louvi A, Onorati M. Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors. ELife 2023, 12: e81716. PMID: 37272619, PMCID: PMC10241521, DOI: 10.7554/elife.81716.Peer-Reviewed Original ResearchConceptsHuman fetal brain tissueStructural brain abnormalitiesC-terminal truncating mutationsFetal brain tissueEtiology of microcephalySevere neurodevelopmental abnormalitiesStem cellsNeuroepithelial stem cellsHuman neural progenitorsHuman brain developmentBrain abnormalitiesCommon causeNeurodevelopmental abnormalitiesAutosomal recessive primary microcephalyBrain tissueBrain developmentCerebral organoidsMicrocephalyUnaffected parentsTruncating mutationsNeural progenitorsHuman neurodevelopmentAbnormalitiesPleiotropic functionsCritical hub
2022
Region Specific Brain Organoids to Study Neurodevelopmental Disorders
Susaimanickam PJ, Kiral FR, Park IH. Region Specific Brain Organoids to Study Neurodevelopmental Disorders. International Journal Of Stem Cells 2022, 15: 26-40. PMID: 35220290, PMCID: PMC8889336, DOI: 10.15283/ijsc22006.Peer-Reviewed Original Research
2019
Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls
Ghatak S, Dolatabadi N, Trudler D, Zhang X, Wu Y, Mohata M, Ambasudhan R, Talantova M, Lipton S. Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. ELife 2019, 8: e50333. PMID: 31782729, PMCID: PMC6905854, DOI: 10.7554/elife.50333.Peer-Reviewed Original ResearchConceptsDisease brainNeuronal culturesHuman Alzheimer's disease brainCerebral organoidsAD-related mutationsHiPSC-derived neuronsTransgenic AD miceInhibitory synaptic activityMechanisms of hyperexcitabilityAlzheimer's disease brainAberrant electrical activitySodium current densityAD micePathophysiological correlatesSynaptic dysfunctionAD pathophysiologyExcessive excitabilitySynaptic activityObserved hyperexcitabilityCognitive declineBursting activityHyperexcitabilityPresenilin 1Electrical activityNeurite length
2018
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Reports 2018, 24: 973-986.e8. PMID: 30044992, PMCID: PMC6178983, DOI: 10.1016/j.celrep.2018.06.100.Peer-Reviewed Original ResearchConceptsExtracellular vesiclesMultivesicular bodiesIntraluminal vesicle formationESCRT proteinsHedgehog secretionProgenitor maintenanceMolecular mechanistic insightsComplex proteinsCell communicationEV subtypesVesicle formationChmp1AAutosomal recessive microcephalyHuman cerebral organoidsSonic hedgehogProgenitor proliferationFunction mutationsImpairs secretionAdult functionMechanistic insightsCerebral organoidsNull micePontocerebellar hypoplasiaShhProteinModeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem‐Cell‐Derived Neurons
Chandrasekaran S, Rajarajan P, Akbarian S, Brennand K. Modeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem‐Cell‐Derived Neurons. 2018, 119-157. DOI: 10.1002/9781119283249.ch6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHuman induced pluripotent stem cellsInduced pluripotent stem cell-derived neuronsPluripotent stem cell-derived neuronsStem cell-derived neuronsZika virus epidemicPathophysiological mechanismsNeurological diseasesInduction protocolNeuropsychiatric diseasesCerebral organoidsTranslational benefitsVirus epidemicDrug testingDisease treatmentInduced pluripotent stem cellsDiseaseNeuronsStem cellsOptimization of differentiationPluripotent stem cellsSpecific subsetNeuroscience researchCulture dishesTransplantationBrain
2017
Cerebral organoids reveal early cortical maldevelopment in schizophrenia—computational anatomy and genomics, role of FGFR1
Stachowiak E, Benson C, Narla S, Dimitri A, Chuye L, Dhiman S, Harikrishnan K, Elahi S, Freedman D, Brennand K, Sarder P, Stachowiak M. Cerebral organoids reveal early cortical maldevelopment in schizophrenia—computational anatomy and genomics, role of FGFR1. Translational Psychiatry 2017, 7: 6. PMID: 30446636, PMCID: PMC5802550, DOI: 10.1038/s41398-017-0054-x.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsCerebral organoidsSchizophrenia patientsVentricular zoneInduced pluripotent stem cellsCortical neuronal maturationUtero brain developmentRole of FGFR1Stem cellsIntracortical connectivityFirst trimesterCortical maldevelopmentCortical malformationsPreventive treatmentCalretinin interneuronsNeuronal maturationSubcortical regionsControl individualsPioneer neuronsCortical zoneBrain developmentHuman embryonic stem cellsProgenitor cellsIntegrative nuclear FGFR1FGFR1 gene
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