2023
STRA6 is essential for induction of vascular smooth muscle lineages in human embryonic cardiac outflow tract development
Zhou C, Häneke T, Rohner E, Sohlmér J, Kameneva P, Artemov A, Adameyko I, Sahara M. STRA6 is essential for induction of vascular smooth muscle lineages in human embryonic cardiac outflow tract development. Cardiovascular Research 2023, 119: 1202-1217. PMID: 36635482, PMCID: PMC10202647, DOI: 10.1093/cvr/cvad010.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsHuman cardiogenesisWild-type human embryonic stem cellsSmooth muscle cellsCardiac outflow tract developmentSingle-cell RNA sequencing datasetsRARα/RXRαCardiogenic transcription factorsRNA sequencing datasetsSmooth muscle lineageRetinoic acid signalingEmbryonic stem cellsVascular smooth muscle lineageRNA-seq dataOutflow tract developmentCardiac outflow tractOFT formationHeart progenitorsMuscle lineageSTRA6 mutationsRas signalingMurine embryonic heartTranscription factorsAcid signalingHeart development
2020
Genome-wide CRISPR screen identifies ZIC2 as an essential gene that controls the cell fate of early mesodermal precursors to human heart progenitors
Xu J, Zhou C, Foo K, Yang R, Xiao Y, Bylund K, Sahara M, Chien K. Genome-wide CRISPR screen identifies ZIC2 as an essential gene that controls the cell fate of early mesodermal precursors to human heart progenitors. Stem Cells 2020, 38: 741-755. PMID: 32129551, PMCID: PMC7891398, DOI: 10.1002/stem.3168.Peer-Reviewed Original ResearchConceptsHuman pluripotent stem cellsCRISPR knockout screensCell fateProgenitor formationEssential genesHuman cardiogenesisGenome-wide CRISPR knockout screenProgenitor cell fate determinationEarly mesodermal precursorsSingle-cell RNA-seq analysisMesoderm precursor cellsCell fate determinationDevelopmental signaling cascadesProgenitor cell fateRNA-seq analysisRNA-seq profilingMultiple gene setsPluripotent stem cellsMesoderm formationMesodermal precursorsHeart progenitorsCommitted stepMesodermal formationGene setsMaster regulator
2018
Lnc’ed in to Cardiogenesis
Sahara M, Eroglu E, Chien K. Lnc’ed in to Cardiogenesis. Cell Stem Cell 2018, 22: 787-789. PMID: 29859167, DOI: 10.1016/j.stem.2018.05.012.Commentaries, Editorials and Letters
2015
Angiogenic potential of early and late outgrowth endothelial progenitor cells is dependent on the time of emergence
Minami Y, Nakajima T, Ikutomi M, Morita T, Komuro I, Sata M, Sahara M. Angiogenic potential of early and late outgrowth endothelial progenitor cells is dependent on the time of emergence. International Journal Of Cardiology 2015, 186: 305-314. PMID: 25838182, DOI: 10.1016/j.ijcard.2015.03.166.Peer-Reviewed Original ResearchConceptsLate outgrowth endothelial progenitor cellsHuman peripheral blood mononuclear cellsLate-outgrowth EPCsEndothelial progenitor cellsEPC subpopulationsHigh angiogenic potentialAngiogenic potentialEarly outgrowth endothelial progenitor cellsDay 17Day 10Unilateral hindlimb ischemia surgeryPeripheral blood mononuclear cellsOutgrowth endothelial progenitor cellsTherapeutic angiogenic potentialProgenitor cellsBlood flow recoveryBlood mononuclear cellsTube formation capabilityVivo therapeutic efficacyIschemic legCollateral formationMononuclear cellsIschemia surgeryParacrine effectsDay 3
2014
Manipulation of a VEGF-Notch signaling circuit drives formation of functional vascular endothelial progenitors from human pluripotent stem cells
Sahara M, Hansson E, Wernet O, Lui K, Später D, Chien K. Manipulation of a VEGF-Notch signaling circuit drives formation of functional vascular endothelial progenitors from human pluripotent stem cells. Cell Research 2014, 24: 820-841. PMID: 24810299, PMCID: PMC4085760, DOI: 10.1038/cr.2014.59.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBone Morphogenetic Protein 4CadherinsCell DifferentiationCell LineEmbryonic Stem CellsEndothelial CellsEndothelium, VascularGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMicePluripotent Stem CellsReceptors, NotchSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsHuman pluripotent stem cellsPluripotent stem cellsEndothelial lineage cellsEndothelial progenitorsLineage cellsStem cellsVascular endothelial progenitorsVE-cadherin promoterEndothelial cellsGreen fluorescent protein expressionFluorescent protein expressionBioactive small moleculesFunctional vessel networksMesodermal precursorsReporter cell lineDrive formationEndothelial lineageGSK-3β inhibitorDifferentiation protocolsMature endothelial cellsAttractive cell populationRapid large-scale productionEfficient differentiationEndothelial differentiationPharmaceutical inhibition
2013
Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation
Sahara M, Ikutomi M, Morita T, Minami Y, Nakajima T, Hirata Y, Nagai R, Sata M. Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation. Cardiovascular Research 2013, 101: 236-246. PMID: 24193738, DOI: 10.1093/cvr/cvt245.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin-Converting Enzyme 2AnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCell ProliferationCells, CulturedDisease Models, AnimalFemoral ArteryGene DeletionGenetic Predisposition to DiseaseInflammation MediatorsJNK Mitogen-Activated Protein KinasesMacrophagesMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaPeptidyl-Dipeptidase APhenotypePlaque, AtheroscleroticProtein Kinase InhibitorsRNA InterferenceSignal TransductionTransfectionVascular System InjuriesConceptsVascular smooth muscle cellsAortic vascular smooth muscle cellsArterial neointima formationVascular diseaseACE2 deficiencyVascular lesionsEnzyme 2Neointima formationApolipoprotein E knockout miceVascular cell adhesion moleculeACE2 KO miceLarge vascular lesionsAngiotensin II levelsRenin-angiotensin systemE knockout miceAortic atherosclerotic plaquesPro-inflammatory phenotypeRole of ACE2Development of atherosclerosisInflammation-related genesArterial neointimal hyperplasiaTumor necrosis factorSmooth muscle cellsPrimary bone marrow macrophagesDeletion of angiotensinA HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells
Später D, Abramczuk M, Buac K, Zangi L, Stachel M, Clarke J, Sahara M, Ludwig A, Chien K. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nature Cell Biology 2013, 15: 1098-1106. PMID: 23974038, DOI: 10.1038/ncb2824.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCell DifferentiationCell LineageCyclic Nucleotide-Gated Cation ChannelsEmbryo, MammalianEmbryonic Stem CellsGene Expression Regulation, DevelopmentalHeart AtriaHeart VentriclesHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMesodermMiceMorphogenesisMuscle ProteinsMyocardiumMyocytes, CardiacPluripotent Stem CellsPotassium ChannelsConceptsHeart fieldFirst heart fieldHuman embryonic stem cellsSecond heart fieldStem cellsEmbryonic stem cellsHuman pluripotent stem cellsPluripotent stem cellsMesodermal cellsDifferentiation culturesCardiomyogenic lineageCardiomyogenic progenitorsMammalian heartProgenitorsLineagesDistinct groupsHCN4CellsMarkers
2011
The ATP-Binding Cassette Transporter ABCG2 Protects Against Pressure Overload–Induced Cardiac Hypertrophy and Heart Failure by Promoting Angiogenesis and Antioxidant Response
Higashikuni Y, Sainz J, Nakamura K, Takaoka M, Enomoto S, Iwata H, Tanaka K, Sahara M, Hirata Y, Nagai R, Sata M. The ATP-Binding Cassette Transporter ABCG2 Protects Against Pressure Overload–Induced Cardiac Hypertrophy and Heart Failure by Promoting Angiogenesis and Antioxidant Response. Arteriosclerosis Thrombosis And Vascular Biology 2011, 32: 654-661. PMID: 22116099, DOI: 10.1161/atvbaha.111.240341.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntioxidantsATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersCells, CulturedDisease Models, AnimalEndothelial CellsGenotypeGlutathioneHeart FailureHindlimbHumansHypertrophy, Left VentricularIschemiaMaleMiceMice, KnockoutMuscle, SkeletalMyocytes, CardiacNeoplasm ProteinsNeovascularization, PhysiologicOxidative StressPhenotypeRatsRats, WistarRNA InterferenceTime FactorsTransfectionVentricular FunctionVentricular RemodelingConceptsTransverse aortic constrictionWild-type micePressure overload-induced cardiac hypertrophyMicrovascular endothelial cellsOverload-induced cardiac hypertrophyCardiac hypertrophyHeart failureEndothelial cellsCassette transporter subfamily G member 2Exaggerated cardiac hypertrophyAntioxidant responseG member 2Tissue defense mechanismsSuperoxide dismutase mimeticCassette transporter ABCG2Cardiac dysfunctionImportant endogenous antioxidantPressure overloadVentricular remodelingAortic constrictionFunctional impairmentATP-Binding Cassette Transporter ABCG2Cardiomyocyte hypertrophyImpaired angiogenesisDismutase mimetic
2010
The ATP-Binding Cassette Transporter BCRP1/ABCG2 Plays a Pivotal Role in Cardiac Repair After Myocardial Infarction Via Modulation of Microvascular Endothelial Cell Survival and Function
Higashikuni Y, Sainz J, Nakamura K, Takaoka M, Enomoto S, Iwata H, Sahara M, Tanaka K, Koibuchi N, Ito S, Kusuhara H, Sugiyama Y, Hirata Y, Nagai R, Sata M. The ATP-Binding Cassette Transporter BCRP1/ABCG2 Plays a Pivotal Role in Cardiac Repair After Myocardial Infarction Via Modulation of Microvascular Endothelial Cell Survival and Function. Arteriosclerosis Thrombosis And Vascular Biology 2010, 30: 2128-2135. PMID: 20829509, DOI: 10.1161/atvbaha.110.211755.Peer-Reviewed Original ResearchConceptsBreast cancer resistance protein 1BCRP1/ABCG2Myocardial infarctionWT miceCardiac repairEndothelial cellsEndothelial cell survivalAbcg2 knockout micePeri-infarction areaMember 2 expressionTissue defense mechanismsMicrovascular endothelial cellsCell survivalResistance protein 1Cardiac ruptureIntracellular protoporphyrin IXVentricular remodelingKO micePivotal roleHistological assessmentKnockout miceSurvival rateABCG2 inhibitionMiceOxidative stressA Phosphodiesterase-5 Inhibitor Vardenafil Enhances Angiogenesis Through a Protein Kinase G-Dependent Hypoxia-Inducible Factor-1/Vascular Endothelial Growth Factor Pathway
Sahara M, Sata M, Morita T, Nakajima T, Hirata Y, Nagai R. A Phosphodiesterase-5 Inhibitor Vardenafil Enhances Angiogenesis Through a Protein Kinase G-Dependent Hypoxia-Inducible Factor-1/Vascular Endothelial Growth Factor Pathway. Arteriosclerosis Thrombosis And Vascular Biology 2010, 30: 1315-1324. PMID: 20413734, DOI: 10.1161/atvbaha.109.201327.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsCapillariesCell HypoxiaCell MovementCells, CulturedCollateral CirculationCyclic GMPCyclic GMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 5Disease Models, AnimalEndothelial CellsGreen Fluorescent ProteinsHindlimbHumansHypoxia-Inducible Factor 1, alpha SubunitImidazolesIschemiaMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutMice, TransgenicMuscle, SkeletalNeovascularization, PhysiologicNitric Oxide Synthase Type IIIPhosphodiesterase 5 InhibitorsPhosphodiesterase InhibitorsPiperazinesRecovery of FunctionRegional Blood FlowRNA InterferenceSignal TransductionStem CellsSulfonesTime FactorsTransfectionTriazinesVardenafil DihydrochlorideVascular Endothelial Growth Factor AConceptsEndothelial progenitor cellsVascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayIschemia-induced angiogenesisGrowth factor pathwaysIschemic muscleMobilization of EPCsSca-1/flkFactor pathwaySoluble guanylate cyclase inhibitorEndothelial nitric oxide synthasePhosphodiesterase-5 inhibitor vardenafilRight femoral arteryBlood flow recoveryEffect of vardenafilPhosphodiesterase-5 inhibitionUnilateral hindlimb ischemiaGuanylate cyclase inhibitorVascular endothelial growth factorNitric oxide synthaseUpregulated protein expressionProtein kinase G inhibitorIschemic cardiovascular diseaseCapillary-like tube formationEndothelial growth factor
2005
Comparison of Various Bone Marrow Fractions in the Ability to Participate in Vascular Remodeling After Mechanical Injury
Sahara M, Sata M, Matsuzaki Y, Tanaka K, Morita T, Hirata Y, Okano H, Nagai R. Comparison of Various Bone Marrow Fractions in the Ability to Participate in Vascular Remodeling After Mechanical Injury. Stem Cells 2005, 23: 874-878. PMID: 15941860, DOI: 10.1634/stemcells.2005-0012.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsGreen fluorescent proteinGFP-positive cellsBone marrow cellsTotal bone marrow cellsMarrow cellsFluorescent proteinCell typesBone marrow fractionLin- cellsSca-1Stem cellsVascular cellsMechanical injuryMarrow fractionsCellsHSC cellsBroad potentialBone marrow reconstitutionPluripotencyVascular remodelingLesion formationRecent reportsProteinTransdifferentiation