2023
Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability
Zhang J, Wu Q, Hu X, Wang Y, Lu J, Chakraborty R, Martin K, Guo S. Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability. Stem Cells 2023, 41: 907-915. PMID: 37386941, PMCID: PMC11009695, DOI: 10.1093/stmcls/sxad051.Peer-Reviewed Original ResearchConceptsMouse pluripotent stem cellsSerum response factorPluripotent stem cellsCell fate stabilityRole of SRFGene expression noiseHeterogeneous gene expressionResponse factorStem cellsNaïve pluripotencyCell state heterogeneityLineage primingExpression noiseActin dynamicsCellular statesPluripotent cellsSRF functionCell statesMechanical signalingGene expressionFunctional modulationCentral mediatorSerum-containing culturesState heterogeneityCellsSex hormones impact early maturation and immune response in the arteriovenous fistula mouse model
Satam K, Ohashi Y, Thaxton C, Gonzalez L, Setia O, Bai H, Aoyagi Y, Xie Y, Zhang W, Yatsula B, Martin K, Cai Y, Dardik A. Sex hormones impact early maturation and immune response in the arteriovenous fistula mouse model. AJP Heart And Circulatory Physiology 2023, 325: h77-h88. PMID: 37145957, PMCID: PMC10243550, DOI: 10.1152/ajpheart.00049.2023.Peer-Reviewed Original ResearchConceptsIntact female miceAVF maturationSex hormonesT cellsFemale miceArteriovenous fistulaMale miceMouse modelHigher IL-10Arteriovenous fistula creationImmune cell recruitmentSex-specific therapiesHormone receptor signalingSex differencesHuman AVF maturationAVF surgeryMale patientsClinical outcomesFemale patientsFistula maturationIL-10C57BL/6 miceInferior outcomesVenous adaptationFistula creationThe age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosis“Cre”ating New Tools for Smooth Muscle Analysis
O’Brien B, Martin K, Offermanns S. “Cre”ating New Tools for Smooth Muscle Analysis. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: 212-214. PMID: 36601960, PMCID: PMC10112502, DOI: 10.1161/atvbaha.122.318855.Peer-Reviewed Original Research
2021
TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy
Ostriker AC, Xie Y, Chakraborty R, Sizer AJ, Bai Y, Ding M, Song WL, Huttner A, Hwa J, Martin KA. TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy. Circulation 2021, 144: 455-470. PMID: 34111946, PMCID: PMC8643133, DOI: 10.1161/circulationaha.120.050553.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsApoptosisBiomarkersDioxygenasesDisease Models, AnimalDisease SusceptibilityDNA-Binding ProteinsHeart TransplantationHumansImmunohistochemistryInterferon-gammaMiceMice, KnockoutMyocytes, Smooth MuscleSignal TransductionSTAT1 Transcription FactorTunica IntimaVascular DiseasesConceptsCoronary allograft vasculopathyGraft arteriopathyIntimal thickeningCAV progressionRole of TET2VSMC apoptosisTransplant samplesGraft modelHigh-dose ascorbic acidTET2 expressionVSMC phenotypeContext of transplantCoronary blood flowEffect of IFNγTET2 activityTET2 depletionSmooth muscle cell apoptosisVascular smooth muscle cell apoptosisMuscle cell apoptosisAllograft vasculopathyDevastating sequelaeMedial thinningAortic graftHeart transplantTransplant failure
2020
Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation
Zeng Z, Xia L, Fan S, Zheng J, Qin J, Fan X, Liu Y, Tao J, Liu Y, Li K, Ling Z, Bu Y, Martin KA, Hwa J, Liu R, Tang WH. Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation. Circulation 2020, 143: 354-371. PMID: 33207953, DOI: 10.1161/circulationaha.120.049715.Peer-Reviewed Original ResearchConceptsHuman coronary artery smooth muscle cellsTet2 knockout miceCoronary artery smooth muscle cellsArtery smooth muscle cellsCircular RNAsSmooth muscle cellsVascular smooth muscle cellsWire-injured mouse femoral arteriesSmooth muscle cell differentiationCircular RNA profilingMuscle cell differentiationRNA sequencing dataLoss of TET2Coronary heart diseaseVascular SMC differentiationMiR-22-3pPlatelet-derived growth factorKnockout miceSMC differentiationMaster regulatorRNA sequencingRNA profilingPlatelet-derived growth factor-BBGene expressionSequencing data
2019
Promoters to Study Vascular Smooth Muscle
Chakraborty R, Saddouk FZ, Carrao AC, Krause DS, Greif DM, Martin KA. Promoters to Study Vascular Smooth Muscle. Arteriosclerosis Thrombosis And Vascular Biology 2019, 39: 603-612. PMID: 30727757, PMCID: PMC6527360, DOI: 10.1161/atvbaha.119.312449.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell LineCell LineageCell TransdifferentiationGene Expression RegulationGene Knockout TechniquesGene TargetingHumansMiceMicrofilament ProteinsMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleMyofibroblastsMyosin Heavy ChainsNeovascularization, PathologicNeovascularization, PhysiologicPhenotypePromoter Regions, GeneticRecombinant Fusion ProteinsConceptsSmooth muscle cellsCre driver linesDiversity of phenotypesMuscle cell typesVisceral smooth muscle cellsSMC transdifferentiationActa2 promoterRemarkable plasticityExciting new eraSMC functionCell typesCre linesEmbryonic heartExciting discoveriesPhenotypeMuscle cellsPerivascular adipocytesPromoterVascular smooth muscleNonmuscular cellsExpressionMyeloid cellsCardiovascular phenotypesCellsBlood vessel wall
2018
TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia
Srivastava R, Rolyan H, Xie Y, Li N, Bhat N, Hong L, Esteghamat F, Adeniran A, Geirsson A, Zhang J, Ge G, Nobrega M, Martin KA, Mani A. TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia. Arteriosclerosis Thrombosis And Vascular Biology 2018, 39: 250-262. PMID: 30567484, PMCID: PMC6365015, DOI: 10.1161/atvbaha.118.311830.Peer-Reviewed Original ResearchConceptsInjury-induced intimal hyperplasiaIntimal hyperplasiaObstructive coronary artery diseaseVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationVascular Smooth Muscle Cell PlasticityLRP6 mutant miceOverexpression of TCF7L2Coronary artery diseaseVascular smooth muscle cellsMultiple mouse modelsMuscle cell dedifferentiationWild-type littermatesSmooth muscle cellsRole of TCF7L2Smooth Muscle Cell PlasticityVascular smooth muscle cell differentiationMuscle cell plasticitySmooth muscle cell differentiationArtery diseaseSM-MHCMouse modelCell cycle inhibitorsHaploinsufficient miceHyperplasia
2017
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, Wu CL, Sano S, Muralidharan S, Rius C, Vuong J, Jacob S, Muralidhar V, Robertson AA, Cooper MA, Andrés V, Hirschi KK, Martin KA, Walsh K. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 2017, 355: 842-847. PMID: 28104796, PMCID: PMC5542057, DOI: 10.1126/science.aag1381.Peer-Reviewed Original ResearchConceptsTET2-deficient cellsLow-density lipoprotein receptor-deficient miceLipoprotein receptor-deficient miceClonal hematopoiesisBlood cellsAtherosclerotic cardiovascular diseaseAtherosclerotic plaque sizeReceptor-deficient miceBone marrow reconstitutionInterleukin-1β secretionMutant blood cellsAtherosclerosis developmentNLRP3 inhibitorAtheroprotective activityCardiovascular diseaseMarrow reconstitutionChimeric micePlaque sizeClonal expansionMiceMarked increaseCausal roleTET2 deficiencySomatic mutationsHematopoietic cells
2015
Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition
Xie Y, Jin Y, Merenick BL, Ding M, Fetalvero KM, Wagner RJ, Mai A, Gleim S, Tucker DF, Birnbaum MJ, Ballif BA, Luciano AK, Sessa WC, Rzucidlo EM, Powell RJ, Hou L, Zhao H, Hwa J, Yu J, Martin KA. Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition. Science Signaling 2015, 8: ra44. PMID: 25969542, PMCID: PMC4560350, DOI: 10.1126/scisignal.2005482.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationGATA6 Transcription FactorHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultiprotein ComplexesMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesConceptsGATA-6Vascular smooth muscle cell differentiationSmooth muscle cell differentiationPhosphorylation-deficient mutantDifferentiation of VSMCsRapamycin complex 1Downstream transcriptional targetsTranscription factor GATA-6Muscle cell differentiationInhibition of mTORC1VSMC hyperplasiaTransactivation of promotersTranscriptional targetsVSMC differentiationNuclear accumulationInduced phosphorylationMechanistic targetReversible differentiationCell differentiationCells undergoDrug targetsInhibition of proliferationPhosphorylationWild-type miceMTORC1
2013
Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity
Liu R, Jin Y, Tang WH, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA. Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity. Circulation 2013, 128: 2047-2057. PMID: 24077167, PMCID: PMC3899790, DOI: 10.1161/circulationaha.113.002887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCell DifferentiationCells, CulturedDioxygenasesDNA-Binding ProteinsEpigenesis, GeneticHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNuclear ProteinsPromoter Regions, GeneticProto-Oncogene ProteinsTrans-ActivatorsWound HealingConceptsTen-Eleven Translocation-2SMC differentiationTET2 knockdownSmooth muscle cellsGene expressionTranslocation 2Smooth Muscle Cell PlasticityMaster epigenetic regulatorSMC gene expressionContractile gene expressionMuscle cell plasticityDedifferentiated smooth muscle cellsTET2 overexpressionContractile smooth muscle cellsHuman smooth muscle cellsChromatin accessibilityEpigenetic landscapeSMC plasticityChromatin immunoprecipitationEpigenetic regulatorsEpigenetic mechanismsCell plasticityMaster regulatorSMC phenotypeTranscriptional upregulation
2010
Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors
Fei D, Li H, Kozul C, Black K, Singh S, Gosse J, DiRenzo J, Martin K, Wang B, Hamilton J, Karagas M, Robbins D. Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors. Cancer Research 2010, 70: 1981-1988. PMID: 20179202, PMCID: PMC2831120, DOI: 10.1158/0008-5472.can-09-2898.Peer-Reviewed Original ResearchConceptsArsenic exposureBladder cancerEnvironmental toxicant arsenicBladder cancer patientsSignificant health problemVariety of tumorsHedgehog signalingCancer patientsHealth problemsHigh levelsTumor samplesCancerHedgehog activitySame cancerHuman carcinogenesisMillions of peopleEtiologyTumorsExposureProgressionHedgehogTissue culture cellsActivationSignalingPatients
2006
Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways
Liu L, Li F, Cardelli J, Martin K, Blenis J, Huang S. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene 2006, 25: 7029-7040. PMID: 16715128, DOI: 10.1038/sj.onc.1209691.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCattleCell Cycle ProteinsCell LineCell MovementCytoprotectionDown-RegulationEnzyme ActivationHumansInsulin-Like Growth Factor IMicePhosphoproteinsPhosphorylationProtein KinasesRibosomal Protein S6 Kinases, 70-kDaSerumSignal TransductionSirolimusTOR Serine-Threonine KinasesTranscription FactorsConceptsCell motilityRNA interferenceEukaryotic initiation factor 4EDownregulation of RaptorType I insulin-like growth factorMTOR kinase activityInitiation factor 4ES6 kinase 1Rapamycin inhibitionTumor cell motilityResistant mutantsSuppression of mTORP70 S6K1Kinase activityKinase 1S6K1Mammalian targetRapamycinProtein 1Effect of rapamycinConsequence of inhibitionCell linesMutantsRaptorsMotility
2004
Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy
McMullen J, Shioi T, Zhang L, Tarnavski O, Sherwood M, Dorfman A, Longnus S, Pende M, Martin K, Blenis J, Thomas G, Izumo S. Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy. Molecular And Cellular Biology 2004, 24: 6231-6240. PMID: 15226426, PMCID: PMC434247, DOI: 10.1128/mcb.24.14.6231-6240.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAortaCardiomegalyFemaleFetusGene Expression Regulation, DevelopmentalMiceMice, KnockoutMice, TransgenicOrgan SizePhosphatidylinositol 3-KinasesPhysical Conditioning, AnimalReceptor, IGF Type 1Ribosomal Protein S6 Kinases, 90-kDaSignal TransductionSirolimusStress, MechanicalSwimmingConceptsRibosomal S6 kinaseS6 kinaseOverexpression of S6K1PI3K mutantCritical downstream effectorRibosomal proteinsTransgenic miceCardiac hypertrophyDownstream effectorsK mutantS6KsGrowth factor pathwaysGenetic relationshipsPathological stressProtein synthesisCritical effectorS6K1K pathwayIGF1 receptorFactor 1Factor pathwayPhysiological stressInsulin-like growth factor-1Physiological stimuliKinase
1994
The mouse creatine kinase paired E-box element confers muscle-specific expression to a heterologous promoter embryonic chicken primary cell culture; CAT assay; luciferase assay; human growth hormone assay
Martin K, Walsh K, Mader S. The mouse creatine kinase paired E-box element confers muscle-specific expression to a heterologous promoter embryonic chicken primary cell culture; CAT assay; luciferase assay; human growth hormone assay. Gene 1994, 142: 275-278. PMID: 8194764, DOI: 10.1016/0378-1119(94)90274-7.Peer-Reviewed Original Research