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 ResearchMeSH KeywordsBody PatterningBrainCell LineHedgehog ProteinsHumansInduced Pluripotent Stem CellsNeuronsOrganoidsWnt ProteinsWnt Signaling PathwayConceptsGradient 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 linesMulticilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions
Mao S, Song R, Jin S, Pang S, Jovanovic A, Zimmerman A, Li P, Wu X, Wendland M, Lin K, Chen W, Choksi S, Chen G, Holtzman M, Reiter J, Wan Y, Xuan Z, Xiang Y, Xu C, Upadhyayula S, Hess H, He L. Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions. Cell Reports 2025, 44: 115383. PMID: 40057957, DOI: 10.1016/j.celrep.2025.115383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAquaporin 1Choroid PlexusCiliaHedgehog ProteinsHydrocephalusMiceSignal TransductionConceptsCSF productionChoroid plexusCerebrospinal fluidSonic hedgehog signalingWater channel AQP1Increased CSF productionHedgehog signalingChoroid plexus functionMotile ciliaMulticiliaSensory ciliaShh signalingNeonatal hydrocephalusSonic hedgehogCiliary lengthRegulate CSF productionSignal intensityCiliary ultrastructureChoroidEpithelial monolayersAQP1Developmental dynamicsCiliaATP1A2Plexus
2024
Developing expert consensus for the use of hedgehog inhibitors in basal cell nevus syndrome
Lukowiak T, Cahn B, Samie F, Leffell D, Oro A, Kibbi N, Kheterpal M, Babakoohi S, Khushalani N, Stephenson A, Ma M, Shi V, Ahmed A, Koza E, Haq M, Yi M, Nadir U, Yoo S, Brieva J, Lucas J, Haber R, Alam M. Developing expert consensus for the use of hedgehog inhibitors in basal cell nevus syndrome. Archives Of Dermatological Research 2024, 316: 453. PMID: 38967654, DOI: 10.1007/s00403-024-03157-z.Peer-Reviewed Original ResearchHigh NaCl Concentrations in Water Are Associated with Developmental Abnormalities and Altered Gene Expression in Zebrafish
Seli D, Prendergast A, Ergun Y, Tyagi A, Taylor H. High NaCl Concentrations in Water Are Associated with Developmental Abnormalities and Altered Gene Expression in Zebrafish. International Journal Of Molecular Sciences 2024, 25: 4104. PMID: 38612913, PMCID: PMC11012806, DOI: 10.3390/ijms25074104.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium ChlorideEcosystemGene ExpressionHedgehog ProteinsLarvaPerciformesSodium ChlorideSodium Chloride, DietaryWaterZebrafishConceptsNaCl concentrationGene expressionIncreasing NaCl concentrationATM signaling pathwayUninflated swim bladderSwim bladder developmentHigh NaCl concentrationsEmbryo growthAssociated with developmental abnormalitiesSwim bladderLarval stageEarly embryo growthEmbryonic deathDevelopmental abnormalitiesSignaling pathwayDevelopment of zebrafishGenes SHHCalcium chlorideGenesSodium chlorideE3 mediumStages of developmentZebrafish embryosAffected ecosystemsPotassium chlorideModulation of canonical Wnt signaling regulates peribiliary mesenchymal identity during homeostasis and injury
Singh S, Budiman T, Redmond D, Gupta V. Modulation of canonical Wnt signaling regulates peribiliary mesenchymal identity during homeostasis and injury. Hepatology Communications 2024, 8: e0368. PMID: 38251878, PMCID: PMC10805418, DOI: 10.1097/hc9.0000000000000368.Peer-Reviewed Original ResearchConceptsT-box transcription factorTranscription factorsMesenchymal gene expressionSignaling effectorsGene expressionGli transcription factorsGene transcription programUpregulation of TBX2Gain of functionSingle-cell sequencingExtrahepatic bile ductCellular identityTranscriptome analysisTranscriptional programsReceptor-ligand analysisMyofibroblast transdifferentiationIn vivo approachesB-cateninT-boxSignaling pathwayBile ductTbx3 expressionTbx3Primary sclerosing cholangitisBile duct ligation
2023
Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells
Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q, Lopez R, Adelekan-Kamara Y, Fan M, Pober J, Tellides G, Jane-wit D. Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells. Frontiers In Immunology 2023, 14: 1248027. PMID: 37915586, PMCID: PMC10616247, DOI: 10.3389/fimmu.2023.1248027.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesHedgehog ProteinsHumansMiceOrgan TransplantationReperfusion InjuryT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryHuman skin xenograftsSkin xenograftsT cellsPolyfunctional cytokine responsesSolid organ transplantationT cell subsetsResponse of CD4Expression of ICOST cell populationsHumanized mouse modelPeripheral helper cellsAllograft lossIL-21PD-1Reperfusion injuryCytokine responsesVascular inflammationPolyclonal expansionHelper cellsOrgan transplantationMouse modelClinical problemCostimulatory signalsDistinct subsetsSuper-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas
Youngblood M, Erson-Omay Z, Li C, Najem H, Coșkun S, Tyrtova E, Montejo J, Miyagishima D, Barak T, Nishimura S, Harmancı A, Clark V, Duran D, Huttner A, Avşar T, Bayri Y, Schramm J, Boetto J, Peyre M, Riche M, Goldbrunner R, Amankulor N, Louvi A, Bilgüvar K, Pamir M, Özduman K, Kilic T, Knight J, Simon M, Horbinski C, Kalamarides M, Timmer M, Heimberger A, Mishra-Gorur K, Moliterno J, Yasuno K, Günel M. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications 2023, 14: 6279. PMID: 37805627, PMCID: PMC10560290, DOI: 10.1038/s41467-023-41926-y.Peer-Reviewed Original ResearchHepatocellular Adenoma: Report of 2 Cases That Highlight the Relevance of Phenotype-Genotype Correlation in the Pediatric Population
Jiao J, Finberg K, Jain D, Morotti R. Hepatocellular Adenoma: Report of 2 Cases That Highlight the Relevance of Phenotype-Genotype Correlation in the Pediatric Population. Pediatric And Developmental Pathology 2023, 26: 394-403. PMID: 37334553, DOI: 10.1177/10935266231175426.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAdenoma, Liver CellAdolescentbeta CateninCarcinoma, HepatocellularChildGenotypeHedgehog ProteinsHumansLiver NeoplasmsMalePhenotypeConceptsHepatocellular adenomaPediatric populationInflammatory HCASonic hedgehog hepatocellular adenomasYoung type 3Maturity-onset diabetesInflammatory hepatocellular adenomaΒ-catenin-activated hepatocellular adenomaAbernethy malformationPhenotype-genotype correlationClinical historyHCA subtypesH-HCACase 2Case 1Type 3Pathological informationB-HCASubtypesFamily surveillanceLimited studiesMalesHedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells
Jiang B, Wang S, Song G, Jiang Q, Fan M, Fang C, Li X, Soh C, Manes T, Cheru N, Qin L, Ren P, Jortner B, Wang Q, Quaranta E, Yoo P, Geirsson A, Davis R, Tellides G, Pober J, Jane-Wit D. Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells. Science Signaling 2023, 16: eabo3406. PMID: 36943921, PMCID: PMC10061549, DOI: 10.1126/scisignal.abo3406.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryChronic vascular inflammationT cellsNLRP3 inflammasomeVascular inflammationChronic inflammationEndothelial cellsIFN-γ responsesControl T cellsNLRP3 inflammasome activityT memory cellsAllograft vasculopathyVascular sequelaeHuman endothelial cellsCoronary arteryEffector responsesCell-autonomous roleInflammasome activityMouse modelInflammationPatient samplesVigorous recruitmentInflammasomePrimary human cellsImmune signaling
2022
Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids
Brady M, Mariani J, Koca Y, Szekely A, King R, Bloch M, Landeros-Weisenberger A, Leckman J, Vaccarino F. Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids. Molecular Psychiatry 2022, 27: 5007-5019. PMID: 36447010, PMCID: PMC9949887, DOI: 10.1038/s41380-022-01880-5.Peer-Reviewed Original ResearchConceptsTourette syndromeInterneuron deficitsGABAergic interneuronsHealthy controlsNeurodevelopmental underpinningsNeuropathological deficitsBG circuitryNeuropsychiatric disordersDecreased differentiationT patientsInterneuronsAltered expressionPotential mechanismsCilia disruptionSonic hedgehogOrganoidsStem cellsTS individualsPluripotent stem cellsGli transcription factorsDeficitsOrganoid differentiationEarly stagesCholinergicPatientsSegmental basaloid follicular hamartomas derive from a post‐zygotic SMO p.L412F pathogenic variant and express hair follicle development‐related proteins in a pattern that distinguish them from basal cell carcinomas
Atzmony L, Ugwu N, Bercovitch LG, Robinson‐Bostom L, Ko CJ, Myung P, Choate KA. Segmental basaloid follicular hamartomas derive from a post‐zygotic SMO p.L412F pathogenic variant and express hair follicle development‐related proteins in a pattern that distinguish them from basal cell carcinomas. American Journal Of Medical Genetics Part A 2022, 188: 3525-3530. PMID: 35972041, PMCID: PMC9669121, DOI: 10.1002/ajmg.a.62951.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Basal CellHair FollicleHamartomaHedgehog ProteinsHumansSkin DiseasesSkin NeoplasmsSmoothened ReceptorConceptsBasal cell carcinomaCell carcinomaFollicular hamartomaProliferation indexBasaloid skin tumorsSporadic basal cell carcinomasBasaloid follicular hamartomaKi-67 expressionLow proliferation indexCentral nervous systemWhole-exome sequencingSystemic involvementExpression of hedgehogMultiple lesionsSkin tumorsWnt/beta-catenin pathwayBasaloid lesionsNervous systemVariable involvementPathogenic variantsSegmental distributionPost-zygotic mutational eventSOX-9 expressionNormal tissuesExome sequencingNon-cell-autonomous activation of hedgehog signaling contributes to disease progression in a mouse model of renal cystic ciliopathy
Hsieh CL, Jerman SJ, Sun Z. Non-cell-autonomous activation of hedgehog signaling contributes to disease progression in a mouse model of renal cystic ciliopathy. Human Molecular Genetics 2022, 31: 4228-4240. PMID: 35904445, PMCID: PMC9759329, DOI: 10.1093/hmg/ddac175.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCiliopathiesCystsDisease Models, AnimalDisease ProgressionHedgehog ProteinsKidney Diseases, CysticMiceMice, TransgenicConceptsHh pathwayAutonomous activationMesenchymal cellsPolycystic kidney diseaseEpithelial cellsCre miceGli inhibitor GANT61Reporter mouse linePrimary ciliaHH signalingHedgehog signalingPKD pathogenesisArl13bSonic hedgehogMutant kidneysPKD modelPKD progressionHh activationKidney functionKidney diseaseCyst progressionCo-culture systemMouse linesMouse modelDistal nephronDecomposing 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
2021
Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates
Brady MV, Vaccarino FM. Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates. Cells 2021, 10: 914. PMID: 33923415, PMCID: PMC8073580, DOI: 10.3390/cells10040914.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBody PatterningHedgehog ProteinsHumansModels, BiologicalPluripotent Stem CellsProsencephalonSignal TransductionConceptsSonic hedgehogHuman neurodevelopmentHuman pluripotent cellsDiverse cellular compositionRole of SHHMaster regulatorPluripotent cellsCellular phenotypesVentral identityNeural organoidsExpression gradientsOrganoid systemsDisease modelingVitro systemPathway activationModel systemCellular compositionOrganoidsHuman developmentQuestions scientistsHedgehogBiologyRegional specification and complementation with non-neuroectodermal cells in human brain organoids
Tanaka Y, Park IH. Regional specification and complementation with non-neuroectodermal cells in human brain organoids. Journal Of Molecular Medicine 2021, 99: 489-500. PMID: 33651139, PMCID: PMC8026433, DOI: 10.1007/s00109-021-02051-9.Peer-Reviewed Original ResearchAnimalsBrainCellular Reprogramming TechniquesEmbryoid BodiesEndothelial CellsFetusFibroblast Growth Factor 2Hedgehog ProteinsHuman Umbilical Vein Endothelial CellsHumansInduced Pluripotent Stem CellsIntercellular Signaling Peptides and ProteinsMicrogliaNeuronsOrgan SpecificityOrganogenesisOrganoidsRetinaSpinal CordWnt Signaling Pathway
2020
Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
Froidure A, Marchal-Duval E, Homps-Legrand M, Ghanem M, Justet A, Crestani B, Mailleux A. Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis. European Respiratory Review 2020, 29: 190140. PMID: 33208483, PMCID: PMC9488512, DOI: 10.1183/16000617.0140-2019.Peer-Reviewed Original ResearchMeSH KeywordsHedgehog ProteinsHumansIdiopathic Pulmonary FibrosisMyofibroblastsSignal TransductionTransforming Growth Factor betaConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisActivation of developmental pathwaysChronically injured lungTransforming growth factor-bChronic lung injuryStem cell therapyType 2 cell hyperplasiaSonic hedgehog pathwayRemodelling of lung parenchymaGrowth factor BIdiopathic pulmonary fibrosis fibroblastsRegulation of cell transformationLung repairLung injuryCell therapyExpression of pathwaysActivation of developmental signaling pathwaysLung architectureLung parenchymaDevelopmental signaling pathwaysTranscriptional integrityHedgehog pathwayFibrosisLungDLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes
Marquez J, Mann N, Arana K, Deniz E, Ji W, Konstantino M, Mis EK, Deshpande C, Jeffries L, McGlynn J, Hugo H, Widmeier E, Konrad M, Tasic V, Morotti R, Baptista J, Ellard S, Lakhani SA, Hildebrandt F, Khokha MK. DLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes. Journal Of Medical Genetics 2020, 58: 453-464. PMID: 32631816, PMCID: PMC7785698, DOI: 10.1136/jmedgenet-2019-106805.Peer-Reviewed Original ResearchConceptsLoss of ciliaPatient tissuesPatient variantsCongenital heart diseaseMultiple organ systemsMultiple congenital anomaliesDLG5 variantsVariety of pathologiesNephrotic syndromeHeart diseaseCongenital anomaliesRespiratory tractKidney tissueOrgan systemsCystic kidneysPatient phenotypesKidneyDiseaseLimb abnormalitiesUnrelated familiesRescue experimentsCraniofacial malformationsCilia dysfunctionTissue-specific manifestationsTissueHedgehog Signaling Demarcates a Niche of Fibrogenic Peribiliary Mesenchymal Cells
Gupta V, Gupta I, Park J, Bram Y, Schwartz RE. Hedgehog Signaling Demarcates a Niche of Fibrogenic Peribiliary Mesenchymal Cells. Gastroenterology 2020, 159: 624-638.e9. PMID: 32289375, PMCID: PMC8204800, DOI: 10.1053/j.gastro.2020.03.075.Peer-Reviewed Original ResearchConceptsCholestatic injuryStellate cellsLiver tissueStromal cellsLiver diseaseBile ductBiliary treePortal tractsMesenchymal cellsPrimary sclerosing cholangitisAlcoholic liver diseaseEpithelial cellsMyofibroblast phenotypeQuantitative reverse transcription polymerase chain reactionBile duct ligationReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionCanals of HeringControl liver tissueHedgehog signalingSclerosing cholangitisHepatic injuryHepatocellular injuryNonalcoholic steatohepatitisPortal fibroblasts
2019
Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney Disease
Ma M, Legué E, Tian X, Somlo S, Liem KF. Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2019, 30: 2103-2111. PMID: 31451534, PMCID: PMC6830786, DOI: 10.1681/asn.2018121274.Peer-Reviewed Original ResearchConceptsHedgehog pathwayPolycystin-1Polycystin-2Autosomal dominant polycystic kidney diseaseMain causal genePolycystic kidney diseaseKidney cyst formationEpithelial cellsLevels of HedgehogCiliary genesDominant polycystic kidney diseaseMutant mouse kidneysRenal epithelial cellsCausal genesSignal transductionCell signalingGenetic manipulationPrimary ciliaCyst formationMultipass transmembraneHedgehog signalingConditional inactivationUnknown pathwayHedgehogKidney phenotypeHedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia
Shallis RM, Bewersdorf JP, Boddu PC, Zeidan AM. Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia. Expert Review Of Anticancer Therapy 2019, 19: 717-729. PMID: 31422721, DOI: 10.1080/14737140.2019.1652095.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaHh pathway inhibitorsMyeloid leukemiaSurvival of AMLPathway inhibitorHh pathwayPoor-risk diseaseHedgehog pathway inhibitionStem cellsCombination therapyClinical trialsFirst approvalTherapeutic strategiesTherapeutic targetPathway inhibitionHematopoietic stem cellsNeoplasm therapyOlder populationTherapyHedgehog pathwayFurther studiesLeukemiaNormal hematopoiesisAdult stem cellsInhibitors
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