2022
Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing
Kogan P, Wirth F, Tomar A, Darr J, Teperino R, Lahm H, Dreßen M, Puluca N, Zhang Z, Neb I, Beck N, Luzius T, de la Osa de la Rosa L, Gärtner K, Hüls C, Zeidler R, Ramanujam D, Engelhardt S, Wenk C, Holdt L, Mononen M, Sahara M, Cleuziou J, Hörer J, Lange R, Krane M, Doppler S. Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing. Basic Research In Cardiology 2022, 117: 11. PMID: 35258704, PMCID: PMC8902493, DOI: 10.1007/s00395-022-00913-y.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingExtracellular vesiclesRNA sequencingMolecular identityCell typesMitochondria-rich cell typesCardiosphere-derived cellsMitochondria-rich cellsHuman-induced pluripotent stem cellsPluripotent stem cellsCardiac progenitor cellsPro-apoptotic BaxGO termsNon-hematopoietic cellsCardiac developmentTranscriptomic similarityStem cellsProgenitor cellsCellular originNon-myocyte cellsNew specific markerCulture conditionsBiological similaritiesSpecial culture conditionsSequencing
2019
Population and Single-Cell Analysis of Human Cardiogenesis Reveals Unique LGR5 Ventricular Progenitors in Embryonic Outflow Tract
Sahara M, Santoro F, Sohlmér J, Zhou C, Witman N, Leung CY, Mononen M, Bylund K, Gruber P, Chien KR. Population and Single-Cell Analysis of Human Cardiogenesis Reveals Unique LGR5 Ventricular Progenitors in Embryonic Outflow Tract. Developmental Cell 2019, 48: 475-490.e7. PMID: 30713072, DOI: 10.1016/j.devcel.2019.01.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell LineCells, CulturedEmbryonic Stem CellsEndothelial CellsHeart VentriclesHuman Embryonic Stem CellsHumansLIM-Homeodomain ProteinsMice, Inbred C57BLMultipotent Stem CellsMyocardiumMyocytes, CardiacOrganogenesisReceptors, G-Protein-CoupledSingle-Cell AnalysisConceptsCardiac stem/progenitor cellsMultipotent cardiac stem/progenitor cellsCardiac developmentMammalian cardiac developmentSingle-cell RNA-seqComprehensive gene expression profilesGene expression profilesHuman embryonic stemSingle-cell analysisStem/progenitor cellsMammalian cardiogenesisHuman cardiogenesisRNA-seqMorphogenetic processesProximal outflow tractEmbryonic stemEmbryonic outflow tractExpression profilesVentricular progenitorsPutative originHuman embryonic heartCardiac cellsEmbryonic heartProgenitor cellsCardiac derivatives
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
Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA
Lui K, Zangi L, Silva E, Bu L, Sahara M, Li R, Mooney D, Chien K. Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA. Cell Research 2013, 23: 1172-1186. PMID: 24018375, PMCID: PMC3790234, DOI: 10.1038/cr.2013.112.Peer-Reviewed Original ResearchConceptsEndothelial specificationHeart progenitorsEndothelial cell fateCell fate decisionsCell fate switchHuman embryonic stem cellsCell-specific genesStem cellsEmbryonic stem cellsHuman pluripotent stem cellsEndothelial cell lineagesPluripotent stem cellsLarge-scale derivationCell fateMammalian cardiogenesisCardiovascular progenitorsMultipotent progenitorsHuman ESCsRegenerative therapeutic potentialCell lineagesEfficient expressionDistinct familiesAngiocrine factorsIsl1Endothelial intermediate
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