2025
PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors
DeSpenza T, Kiziltug E, Allington G, Barson D, McGee S, O’Connor D, Robert S, Mekbib K, Nanda P, Greenberg A, Singh A, Duy P, Mandino F, Zhao S, Lynn A, Reeves B, Marlier A, Getz S, Nelson-Williams C, Shimelis H, Walsh L, Zhang J, Wang W, Prina M, OuYang A, Abdulkareem A, Smith H, Shohfi J, Mehta N, Dennis E, Reduron L, Hong J, Butler W, Carter B, Deniz E, Lake E, Constable R, Sahin M, Srivastava S, Winden K, Hoffman E, Carlson M, Gunel M, Lifton R, Alper S, Jin S, Crair M, Moreno-De-Luca A, Luikart B, Kahle K. PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors. Nature Neuroscience 2025, 28: 536-557. PMID: 39994410, DOI: 10.1038/s41593-024-01865-3.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsCongenital hydrocephalusCSF dynamicsIncreased CSF productionDe novo mutationsFrequent monogenic causeEverolimus treatmentCSF shuntingNonsurgical treatmentPTEN mutationsAqueductal stenosisInhibitory interneuronsVentriculomegalyProgenitor cellsChoroid plexusMonogenic causeCortical networksIncreased survivalBrain ventriclesCortical deficitsNeural progenitorsGene PTENCSF productionNkx2.1PTEN
2024
Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain development
Liu Y, Luo X, Sun Y, Chen K, Hu T, You B, Xu J, Zhang F, Cheng Q, Meng X, Yan T, Li X, Qi X, He X, Guo X, Li C, Su B. Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain development. Developmental Cell 2024, 60: 414-428.e8. PMID: 39481377, DOI: 10.1016/j.devcel.2024.10.005.Peer-Reviewed Original ResearchEvolutionary changesDistal regulatory elementsGene regulatory mechanismsExtracellular matrixSingle-cell multiomicsProgenitor cellsTranscriptional divergenceEvolutionary divergenceChromatin regionsChromatin accessibilityNeural progenitorsRegulatory elementsSequence changesTranscriptional rewiringGenetic mechanismsMouse prefrontal cortexRegulatory mechanismsPrefrontal cortexHuman neural progenitorsHuman-specific featuresUpper-layer neuronsNeural progenitor cellsChromatinCellular propertiesProgenitor proliferationDysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus
Bertino F, Mukherjee D, Bonora M, Bagowski C, Nardelli J, Metani L, Venturini D, Chianese D, Santander N, Salaroglio I, Hentschel A, Quarta E, Genova T, McKinney A, Allocco A, Fiorito V, Petrillo S, Ammirata G, De Giorgio F, Dennis E, Allington G, Maier F, Shoukier M, Gloning K, Munaron L, Mussano F, Salsano E, Pareyson D, di Rocco M, Altruda F, Panagiotakos G, Kahle K, Gressens P, Riganti C, Pinton P, Roos A, Arnold T, Tolosano E, Chiabrando D. Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus. Cell Reports Medicine 2024, 5: 101647. PMID: 39019006, PMCID: PMC11293339, DOI: 10.1016/j.xcrm.2024.101647.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCalcium handlingNeural progenitor cellsMitochondrial calcium handlingMouse neural progenitor cellsFLVCR1 geneMitochondrial calcium levelsVentricular dilatationLive birthsCalcium levelsProgenitor cellsClinical challengeVentricle enlargementPathogenetic mechanismsSevere formCortical neurogenesisNeural progenitorsFLVCR1aMitochondria-associated membranesHydrocephalusMiceFLVCR1CH genesMolecular mechanismsMetabolic activityLateral expansion of the mammalian cerebral cortex is related to anchorage of centrosomes in apical neural progenitors
Morozov Y, Rakic P. Lateral expansion of the mammalian cerebral cortex is related to anchorage of centrosomes in apical neural progenitors. Cerebral Cortex 2024, 34: bhae293. PMID: 39024157, PMCID: PMC11485267, DOI: 10.1093/cercor/bhae293.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsProgenitor cellsVentricular zoneCerebral cortexBasolateral cell membraneApical anchorageProlonged neurogenesisMammalian cerebral cortexPrimary ciliaApical neural progenitorsCell membraneFraction of cellsNeural progenitorsStem cellsCerebral neurogenesisApical segmentsDevelopment of ciliaNuclear translocationMicrotubule organizing centerNeurogenesisCellsMacaque monkeysSpecies-specific differencesCortexBasal bodiesMassively parallel disruption of enhancers active in human neural stem cells
Geller E, Noble M, Morales M, Gockley J, Emera D, Uebbing S, Cotney J, Noonan J. Massively parallel disruption of enhancers active in human neural stem cells. Cell Reports 2024, 43: 113693. PMID: 38271204, PMCID: PMC11078116, DOI: 10.1016/j.celrep.2024.113693.Peer-Reviewed Original ResearchHuman neural stem cellsNeural stem cellsStem cellsProliferation phenotypeAssociated with neurodevelopmental disordersNeurodevelopmental disordersEnhanced disruptionHuman Accelerated RegionsNeural progenitor proliferationEffects of genetic variationHuman cortical evolutionProgenitor proliferationSelf-renewalNeural progenitorsProgenitor populationsCerebral cortexChromatin interactionsHuman cerebral cortexNeural progenitor populationsGene regulationRegulatory elementsConserved regionGene disruptionGenetic variationRegulatory relationships
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
Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome
Talvio K, Minkeviciene R, Townsley K, Achuta V, Huckins L, Corcoran P, Brennand K, Castrén M. Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome. Frontiers In Cell And Developmental Biology 2022, 10: 1034679. PMID: 36506088, PMCID: PMC9731341, DOI: 10.3389/fcell.2022.1034679.Peer-Reviewed Original ResearchInduced pluripotent stem cellsFragile X syndromeHuman induced pluripotent stem cellsNeural progenitorsX syndromeEarly gene expression changesGene expression changesPatient-derived induced pluripotent stem cellsTriplet repeat instabilityFunctional enrichment analysisHuman neural progenitorsPluripotent stem cellsRNA splicingPhenotypic variationIntellectual disability syndromeEnrichment analysisExpression changesRepeat instabilityMolecular mechanismsProtein resultsGrowth factor pathwaysInsulin-like growth factor (IGF) pathwayAltered expressionStem cellsTranscriptome
2021
Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism
Urresti J, Zhang P, Moran-Losada P, Yu N, Negraes P, Trujillo C, Antaki D, Amar M, Chau K, Pramod A, Diedrich J, Tejwani L, Romero S, Sebat J, Yates III J, Muotri A, Iakoucheva L. Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism. Molecular Psychiatry 2021, 26: 7560-7580. PMID: 34433918, PMCID: PMC8873019, DOI: 10.1038/s41380-021-01243-6.Peer-Reviewed Original ResearchConceptsCortical organoidsCommon copy number variationNeural progenitorsRatio of neuronsPotential neurobiological mechanismsOrganoid sizeEarly brain developmentSynapse numberNeuronal maturationMigration deficitsBrain developmentNeurodevelopmental processesIon channel activityNeurobiological mechanismsNeuron migrationNeocortical developmentSkin fibroblastsChannel activityPatientsEarly neurogenesisMicrocephaly phenotypeNeurite outgrowthNeuronsAutism spectrum disorderSmall GTPase RhoA
2016
Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly
Li H, Bielas SL, Zaki MS, Ismail S, Farfara D, Um K, Rosti RO, Scott EC, Tu S, C. NC, Gabriel S, Erson-Omay EZ, Ercan-Sencicek AG, Yasuno K, Çağlayan AO, Kaymakçalan H, Ekici B, Bilguvar K, Gunel M, Gleeson JG. Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly. American Journal Of Human Genetics 2016, 99: 501-510. PMID: 27453578, PMCID: PMC4974110, DOI: 10.1016/j.ajhg.2016.07.004.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsPrimary microcephalyHuman primary microcephalyAutosomal recessive primary microcephalyNon-progressive intellectual disabilityAmino acid residuesPluripotent stem cellsMitotic cytokinesisCellular functionsGenome editingCell divisionKinase domainAbnormal cytokinesisCRISPR/Homozygous missense mutationCytokinesisKinase activityMultipolar spindlesNeural progenitorsAcid residuesFunction mutationsMissense mutationsStem cellsMultiple rolesMutationsReduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks
Nebel RA, Zhao D, Pedrosa E, Kirschen J, Lachman HM, Zheng D, Abrahams BS. Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PLOS ONE 2016, 11: e0148039. PMID: 26824476, PMCID: PMC4732616, DOI: 10.1371/journal.pone.0148039.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultBase SequenceChromosomes, Human, Pair 15EpilepsyGene Expression ProfilingGene Expression RegulationGene Knockdown TechniquesGene Regulatory NetworksGenetic LociHeterozygoteHumansMaleMiddle AgedMolecular Sequence DataNerve Tissue ProteinsNeural Stem CellsPrimary Cell CultureRiskSchizophreniaSequence DeletionConceptsEpilepsy genesRole of CYFIP1Novel disease candidatesHuman neural progenitorsEpilepsy riskSubset of DEGsPostsynaptic density genesNeuronal differentiationFMRP targetsGene networksNeural progenitorsSchizophreniaCytoskeletal remodelingRNA-seqDeletion carriersKnockdown experimentsVariable expressivityDisease genesProgenitors resultsDisease candidatesGenesCellular assaysCYFIP1DisordersDysregulation
2015
Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors
Mishra-Gorur K, Çağlayan AO, Schaffer AE, Chabu C, Henegariu O, Vonhoff F, Akgümüş GT, Nishimura S, Han W, Tu S, Baran B, Gümüş H, Dilber C, Zaki MS, Hossni HAA, Rivière JB, Kayserili H, Spencer EG, Rosti RÖ, Schroth J, Per H, Çağlar C, Çağlar Ç, Dölen D, Baranoski JF, Kumandaş S, Minja FJ, Erson-Omay EZ, Mane SM, Lifton RP, Xu T, Keshishian H, Dobyns WB, C. NC, Šestan N, Louvi A, Bilgüvar K, Yasuno K, Gleeson JG, Günel M. Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors. Neuron 2015, 85: 228. PMID: 29654772, DOI: 10.1016/j.neuron.2014.12.046.Peer-Reviewed Original ResearchTracking and transforming neocortical progenitors by CRISPR/Cas9 gene targeting and piggyBac transposase lineage labeling
Chen F, Rosiene J, Che A, Becker A, LoTurco J. Tracking and transforming neocortical progenitors by CRISPR/Cas9 gene targeting and piggyBac transposase lineage labeling. Development 2015, 142: 3601-3611. PMID: 26400094, PMCID: PMC4631763, DOI: 10.1242/dev.118836.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBrainBrain NeoplasmsCell LineageChromosomes, Artificial, BacterialCRISPR-Cas SystemsElectroporationFemaleGlioblastomaHumansMutagenesisMutationNeurofibromin 1NeuronsPregnancyPregnancy, AnimalPTEN PhosphohydrolaseRatsRats, WistarStem CellsTransposasesTumor Suppressor Protein p53ConceptsNeurodevelopmental disruptionNeural progenitorsLineage labelingCRISPR/Cas9 gene targetingNeuronal excitabilityDecreased PTEN expressionNeuronal hypertrophyNeocortical progenitorsModel human diseasesTumor formationSomatic mutationsTumorGlioblastoma tumorsPTEN expressionSomatic cellsTumor suppressorNeural developmentProgenitorsGene targetingInduce targeted mutationsHuman diseasesMutationsTargeted mutagenesisCRISPR/Cas9 systemCells
2014
Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss
Lee Y, Brown EJ, Chang S, McKinnon PJ. Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss. Journal Of Neuroscience 2014, 34: 7836-7844. PMID: 24899707, PMCID: PMC4044246, DOI: 10.1523/jneurosci.4245-13.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAtaxia Telangiectasia Mutated Proteinsbeta-GalactosidaseBrainCell CycleCell Cycle ProteinsCells, CulturedDNA DamageDNA-Binding ProteinsEmbryo, MammalianFemaleGene Expression RegulationMaleMiceMice, TransgenicNestinNeuronsShelterin ComplexTelomereTelomere-Binding ProteinsCcm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration
Louvi A, Nishimura S, Günel M. Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration. Development 2014, 141: 1404-1415. PMID: 24595293, PMCID: PMC3943187, DOI: 10.1242/dev.093526.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCell MovementCell ProliferationCyclin-Dependent Kinase 5FemaleHemangioma, Cavernous, Central Nervous SystemIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMice, TransgenicNeocortexNeural Stem CellsNeurogliaPregnancyrho GTP-Binding ProteinsrhoA GTP-Binding ProteinSignal TransductionConceptsCerebral cavernous malformation 3Neuronal migrationCerebral cavernous malformationsRadial glia progenitorsCell non-autonomous functionCerebrovascular disordersPyramidal neuronsCortical plateLaminar positioningSubventricular zoneCortical developmentCavernous malformationsRadial gliaLoss of functionNascent neuronsNeuronal morphologySevere malformationsGlia progenitorsNeural progenitorsNeuronsNon-autonomous functionsMalformationsRhoA pathwayPossible interactionsGlia
2013
Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice
Kusne Y, Goldberg EL, Parker SS, Hapak SM, Maskaykina IY, Chew WM, Limesand KH, Brooks HL, Price TJ, Sanai N, Nikolich-Zugich J, Ghosh S. Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice. GeroScience 2013, 36: 199-212. PMID: 23949159, PMCID: PMC3889877, DOI: 10.1007/s11357-013-9572-5.Peer-Reviewed Original ResearchConceptsSystemic administrationMTOR inhibitorsImproved health spanAdult-born neuronsHealth spanEffects of chronicNeural progenitorsAdult neural stem cellsMTOR inhibitor rapamycinInhibition of mTORPotential adverse effectsAdult neural progenitorsNeural stem cellsSystemic treatmentDendate gyrusMouse hippocampusSubventricular regionOrgan functionMetforminBehavioral healthInhibitor rapamycinAdverse effectsPharmacological inhibitorsMTORRapamycin
2011
Control of Adult-Born Neuron Production by Converging GABA and Glutamate Signals
Platel J, Bordey A. Control of Adult-Born Neuron Production by Converging GABA and Glutamate Signals. 2011, 395-406. DOI: 10.1007/978-4-431-53933-9_17.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSteady-state levelsStem cellsNovel epigenetic controlCell-cell signalingNeuron productionStem cell proliferationEpigenetic controlNeuroblast poolProliferative cuesNeuroblast numbersNeural stem cellsMosaic expressionNeural progenitorsHigh-affinity uptake systemUptake systemAdult-born neuronsHigh turnover rateCell proliferationNeuroblastsControl of adultsNeurotransmitter releaseNegative feedback controlNeuroblast productionImmature neuronsAdult neurogenesis
2009
Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling
Torii M, Hashimoto-Torii K, Levitt P, Rakic P. Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling. Nature 2009, 461: 524-528. PMID: 19759535, PMCID: PMC2874978, DOI: 10.1038/nature08362.Peer-Reviewed Original ResearchConceptsNeocortical excitatory neuronsRadial glial fibersColumnar organizationEphA/ephrinCerebral cortexFunctional impairmentNeuronal clonesExcitatory neuronsGlial fibersTangential migrationCortical columnsNeural progenitorsCircuit developmentEphrinProliferative unitsPopulationClonal populationsCortexNeuronsDifferentiation of Neural Progenitor Cells in a Microfluidic Chip‐Generated Cytokine Gradient
Park J, Kim S, Woo D, Lee E, Kim J, Lee S. Differentiation of Neural Progenitor Cells in a Microfluidic Chip‐Generated Cytokine Gradient. Stem Cells 2009, 27: 2646-2654. PMID: 19711444, DOI: 10.1002/stem.202.Peer-Reviewed Original ResearchConceptsCell typesNeural progenitorsHuman embryonic stem cellsEarly embryonic developmentStem cellsEmbryonic stem cellsCytokine gradientsEnriched populationNeural progenitor cellsPrimitive stem cellsEmbryonic developmentSignaling moleculesDiverse tissuesCell body clustersProgenitor cellsNeurite bundlesGrowth factorProgenitorsCell-friendly microenvironmentCellsDifferentiationExogenous cytokinesImportant roleBody clustersSpatial gradientsDifferentiation of Human Neural Progenitor Cells on PLGA Microfibers
Hwang C, Kim S, Kim J, Khademhosseini A, Lee S. Differentiation of Human Neural Progenitor Cells on PLGA Microfibers. 2009, 1: 1-2. DOI: 10.1109/nebc.2009.4967758.Peer-Reviewed Original ResearchHuman embryonic stem cellsNeural progenitor cellsEmbryoid bodiesMicrofluidic spinning systemPLGA microfibersNeural tissue regenerationEmbryonic stem cellsNeural tissue engineeringProgenitor cellsHuman neural progenitor cellsTissue engineeringNeuronal protein expressionNeural progenitor markersGlial fibrillary acidic proteinMicrofibersTissue regenerationNascent fibersPLGA fibersNeural progenitorsDifferentiated cellsCell differentiationProgenitor markersStem cellsGuidance cuesProtein expression
2008
Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood–spinal cord barrier
Rauch MF, Hynes SR, Bertram J, Redmond A, Robinson R, Williams C, Xu H, Madri JA, Lavik EB. Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood–spinal cord barrier. European Journal Of Neuroscience 2008, 29: 132-145. PMID: 19120441, PMCID: PMC2764251, DOI: 10.1111/j.1460-9568.2008.06567.x.Peer-Reviewed Original ResearchMeSH KeywordsAbsorbable ImplantsAnimalsBlood VesselsBlood-Brain BarrierCells, CulturedCoculture TechniquesDisease Models, AnimalEndothelial CellsFemaleGlycolatesHydrogelsLactic AcidMicrocirculationNeovascularization, PhysiologicPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerRatsRats, Sprague-DawleyRats, TransgenicSpinal CordSpinal Cord InjuriesStem Cell TransplantationTissue EngineeringTissue ScaffoldsTreatment OutcomeConceptsBlood-spinal cord barrierSpinal cord injuryCord injuryNeural progenitor cellsEndothelial cellsPositive stainingRat hemisection modelEndothelial barrier antigenFunctional vesselsRole of angiogenesisInjury epicenterSimilar coculturesSpinal cordNPC groupHemisection modelEC groupVessel densityLesion controlInjuryNeural regenerationProgenitor cellsAngiogenesisNeural progenitorsSubcutaneous modelCoculture
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