2025
Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines
Scuderi S, Kang T, Jourdon A, Nelson A, Yang L, Wu F, Anderson G, Mariani J, Tomasini L, Sarangi V, Abyzov A, Levchenko A, Vaccarino F. Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines. Cell Stem Cell 2025, 32: 970-989.e11. PMID: 40315847, PMCID: PMC12145255, DOI: 10.1016/j.stem.2025.04.006.Peer-Reviewed Original ResearchConceptsGradient of WntGene expression programsSingle-cell transcriptomicsBrain lineagesMorphogen gradientsEpigenetic variationDorso-ventral axisShh signalingExpression programsMorphogenFetal human brainHuman iPSC linesPluripotent stem cellsCell linesNeuronal lineageNeural tubeShhWntLineagesLine-to-line variationEarly patterningPattern systemPattern variationHuman brain regionsIPSC lines
2022
Decomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients
Qu R, Gupta K, Dong D, Jiang Y, Landa B, Saez C, Strickland G, Levinsohn J, Weng PL, Taketo MM, Kluger Y, Myung P. Decomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients. Developmental Cell 2022, 57: 1053-1067.e5. PMID: 35421372, PMCID: PMC9050909, DOI: 10.1016/j.devcel.2022.03.011.Peer-Reviewed Original ResearchConceptsMorphogen gradientsCell fate specificationWnt/β-cateninFate specificationShape tissuesOrgan formationCell fateDermal condensatesGenetic perturbationsNiche formationDifferentiation processSpatiotemporal patterningCell behaviorΒ-cateninMore intermediatesComputational approachProliferationMorphogenesisScRNAOrganogenesisShhKey componentProgenitorsCritical transitionDKK1
2019
Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression
Bar C, Cohen I, Zhao D, Pothula V, Litskevitch A, Koseki H, Zheng D, Ezhkova E. Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression. Cell Reports 2019, 28: 257-266.e5. PMID: 31269445, PMCID: PMC6921245, DOI: 10.1016/j.celrep.2019.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCell CycleChromatin ImmunoprecipitationChromatin Immunoprecipitation SequencingCyclin-Dependent Kinase Inhibitor p16Epigenesis, GeneticEpitheliumGene Expression Regulation, DevelopmentalGene OntologyHedgehog ProteinsMiceMice, KnockoutMicroscopy, Electron, ScanningPolycomb Repressive Complex 1Polycomb Repressive Complex 2RNA-SeqSignal TransductionTaste BudsTongueConceptsGene expressionPolycomb Repressive Complex 1Spatial gene expression patternsRepressive Complex 1Gene expression patternsCell gene expressionChromatin regulatorsTissue patterningSonic hedgehog expressionEpigenetic regulationNiche structureExpression patternsCell genesEpithelial progenitorsHedgehog expressionShhEctopic ShhTaste cellsPapilla structuresTissue patternsExpressionCellsPatterningProper maintenanceComplexes 1
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 hypoplasiaShhProtein
2007
Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis
Morton J, Mongeau M, Klimstra D, Morris J, Lee Y, Kawaguchi Y, Wright C, Hebrok M, Lewis B. Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 5103-5108. PMID: 17372229, PMCID: PMC1828712, DOI: 10.1073/pnas.0701158104.Peer-Reviewed Original ResearchConceptsShh signalingActivation of phosphatidylinositol 3-kinase signalingSonic hedgehogPhosphatidylinositol 3-kinase signalingStability of Bcl-2Pancreatic duct epithelial cellsActivation of sonic hedgehogPancreatic tumorigenesisActivated K-rasDuct epithelial cellsCell cycle regulator cyclin D1Epithelial cellsBcl-x(LTranscriptional regulationRegulator cyclin D1Dependence of tumor cellsPancreatic tumor developmentProliferation of pancreatic duct epithelial cellsBcl-2Signaling pathwayResistance to therapeutic interventionsShhShh expressionCyclin D1Stages of pancreatic carcinogenesis
2002
Regulation of Gli1 Transcriptional Activity in the Nucleus by Dyrk1*
Mao J, Maye P, Kogerman P, Tejedor F, Toftgard R, Xie W, Wu G, Wu D. Regulation of Gli1 Transcriptional Activity in the Nucleus by Dyrk1*. Journal Of Biological Chemistry 2002, 277: 35156-35161. PMID: 12138125, DOI: 10.1074/jbc.m206743200.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCell DifferentiationCell NucleusCOS CellsGene Expression RegulationHedgehog ProteinsMiceOncogene ProteinsPhosphorylationPrecipitin TestsProtein Serine-Threonine KinasesProtein TransportProtein-Tyrosine KinasesSignal TransductionTrans-ActivatorsTranscription FactorsTranscription, GeneticZinc Finger Protein GLI1ConceptsTranscriptional activityGene transcriptionDual-specificity protein kinaseNuclear export mutantGLI1 transcriptional activityMouse C3H10T1/2 cellsReporter gene assayCellular rolesExport mutantsTranscriptional regulationProtein kinaseKinase activityC3H10T1/2 cellsLEF-1Kinase 1DYRK1Sonic hedgehogC-JunGene assayCell nucleiShhTranscriptionRegulationGli1Pathway
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