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
2022
Progress in Bioengineering Strategies for Heart Regenerative Medicine
Häneke T, Sahara M. Progress in Bioengineering Strategies for Heart Regenerative Medicine. International Journal Of Molecular Sciences 2022, 23: 3482. PMID: 35408844, PMCID: PMC8998628, DOI: 10.3390/ijms23073482.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman pluripotent stem cellsCardiac tissue engineering strategiesRegenerative medicineStem cell engineeringHeart regenerationNovel functional biomaterialsCardiac tissue engineeringStem cell biologyTissue engineering strategiesHeart diseasePluripotent stem cellsEngineering strategiesCell engineeringFunctional biomaterialsTissue engineeringCardiac biologyCell biologyBioengineering strategiesGreat promiseCardiomyocyte maturationDisease modelingHeart regenerative medicineInsufficient therapeutic optionsStem cellsTherapeutic applicationsUncovering 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
2021
An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation
Rohner E, Witman N, Sohlmer J, De Genst E, Louch W, Sahara M, Chien K. An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation. Molecular Medicine 2021, 27: 102. PMID: 34496741, PMCID: PMC8425124, DOI: 10.1186/s10020-021-00362-8.Peer-Reviewed Original ResearchConceptsNull mutationMolecular pathwaysProtein analysis toolsBulk RNA sequencingRNA sequencing analysisWild-type reporterDetailed molecular pathwaysDistinct transcriptomic signaturesTranscriptional profilingRNA sequencingProteasomal pathwayHuman embryonic stem cell-derived cardiomyocytesEmbryonic stem cell-derived cardiomyocytesProtein expression levelsProteasomal inhibitionChemical inhibitorsDetectable proteinTranscriptomic signaturesSequencing analysisDegradation contributesMRNA constructsStem cell-derived cardiomyocytesPLN proteinExpression levelsDegradation pathwayIsolation of human ESC-derived cardiac derivatives and embryonic heart cells for population and single-cell RNA-seq analysis
Santoro F, Chien K, Sahara M. Isolation of human ESC-derived cardiac derivatives and embryonic heart cells for population and single-cell RNA-seq analysis. STAR Protocols 2021, 2: 100339. PMID: 33644774, PMCID: PMC7887647, DOI: 10.1016/j.xpro.2021.100339.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cell differentiationEmbryonic stem cell differentiationSingle-cell RNA-seq analysisSingle-cell RNA sequencing analysisComprehensive transcriptional analysisRNA-seq analysisStem cell differentiationRNA sequencing analysisCardiac derivativesFluorescence-activated cell sortingSmart-seq2Developmental tissuesTranscriptional analysisCombination of populationCDNA libraryMolecular atlasHuman embryogenesisHuman ESCsCell differentiationSequencing analysisComplete detailsCell sortingPowerful approachEmbryonic heart cellsDifferentiation
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
2019
Cardiac progenitors and paracrine mediators in cardiogenesis and heart regeneration
Witman N, Zhou C, Grote Beverborg N, Sahara M, Chien K. Cardiac progenitors and paracrine mediators in cardiogenesis and heart regeneration. Seminars In Cell And Developmental Biology 2019, 100: 29-51. PMID: 31862220, DOI: 10.1016/j.semcdb.2019.10.011.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCardiac progenitorsHeart regenerationCardiac progenitor cell biologyMammalian cardiac developmentProgenitor cell biologyParacrine mediatorsMorphogenetic processesCell biologyCardiac developmentMolecular mechanismsCell-free therapyCardiogenesisModern biotechnologyDiseased settingsMammalian heartProgenitorsCongenital heart diseaseRegenerative capabilityTissue engineering platformsRecent knowledgeEngineering platformHeart diseaseNovel toolHeart repairRegenerationIn search of the next super models
Goedel A, Grote Beverborg N, Sahara M, Chien K. In search of the next super models. EMBO Molecular Medicine 2019, 11: emmm201911502. PMID: 31736275, PMCID: PMC6895600, DOI: 10.15252/emmm.201911502.Commentaries, Editorials and LettersCell-mediated delivery of VEGF modified mRNA enhances blood vessel regeneration and ameliorates murine critical limb ischemia
Yu Z, Witman N, Wang W, Li D, Yan B, Deng M, Wang X, Wang H, Zhou G, Liu W, Sahara M, Cao Y, Fritsche-Danielson R, Zhang W, Fu W, Chien K. Cell-mediated delivery of VEGF modified mRNA enhances blood vessel regeneration and ameliorates murine critical limb ischemia. Journal Of Controlled Release 2019, 310: 103-114. PMID: 31425721, DOI: 10.1016/j.jconrel.2019.08.014.Peer-Reviewed Original ResearchPopulation 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
2017
Response to “Comment to the article ‘Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation’”
Ikutomi M, Minami Y, Sahara M. Response to “Comment to the article ‘Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation’”. Journal Of Molecular And Cellular Cardiology 2017, 103: 137-138. PMID: 28109765, DOI: 10.1016/j.yjmcc.2017.01.010.Commentaries, Editorials and Letters
2015
Response to the letter by Guo et al., “Endothelial progenitor cells therapy: From bench to bedside”
Minami Y, Ikutomi M, Sahara M. Response to the letter by Guo et al., “Endothelial progenitor cells therapy: From bench to bedside”. International Journal Of Cardiology 2015, 205: 97-98. PMID: 26730839, DOI: 10.1016/j.ijcard.2015.12.026.Commentaries, Editorials and LettersDiverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation
Ikutomi M, Sahara M, Nakajima T, Minami Y, Morita T, Hirata Y, Komuro I, Nakamura F, Sata M. Diverse contribution of bone marrow-derived late-outgrowth endothelial progenitor cells to vascular repair under pulmonary arterial hypertension and arterial neointimal formation. Journal Of Molecular And Cellular Cardiology 2015, 86: 121-135. PMID: 26231083, DOI: 10.1016/j.yjmcc.2015.07.019.Peer-Reviewed Original ResearchConceptsPulmonary arterial hypertensionEndothelial progenitor cellsLate outgrowth endothelial progenitor cellsEarly endothelial progenitor cellsFemoral arteryVascular repairEPC subpopulationsArterial hypertensionArterial neointimal formationProgenitor cellsBM mononuclear cellsNeointimal lesion formationFisher 344 ratsEPC treatmentEnhanced proliferation potentialPulmonary arteriolesPulmonary arteryPulmonary vasculatureEndovascular injuryMononuclear cellsVascular diseaseSystemic arteriesTherapeutic effectNeointimal formationInflammatory genesAngiogenic 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 3Programming and reprogramming a human heart cell
Sahara M, Santoro F, Chien K. Programming and reprogramming a human heart cell. The EMBO Journal 2015, 34: 710-738. PMID: 25712211, PMCID: PMC4369310, DOI: 10.15252/embj.201490563.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStem cell biologyCardiac regenerative therapeuticsHuman heart cellsCardiac regenerative medicineHuman cardiogenesisMolecular programsCell biologyRegenerative therapeuticsCardiac regenerationHeart cellsRegenerative medicineDevelopmental cardiologyLatest discoveriesNovel therapeutic toolDiseased heartCardiac muscleCellsCardiogenesisTherapeutic strategiesClinical practiceTherapeutic toolBiologyModest outcomesCurrent controversiesDeeper understanding
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 intermediateA 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
2012
Nicorandil Attenuates Monocrotaline-Induced Vascular Endothelial Damage and Pulmonary Arterial Hypertension
Sahara M, Sata M, Morita T, Hirata Y, Nagai R. Nicorandil Attenuates Monocrotaline-Induced Vascular Endothelial Damage and Pulmonary Arterial Hypertension. PLOS ONE 2012, 7: e33367. PMID: 22479390, PMCID: PMC3316574, DOI: 10.1371/journal.pone.0033367.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntihypertensive AgentsApoptosisBlotting, WesternCaspase 3Cells, CulturedDrug Therapy, CombinationEndothelium, VascularEnzyme InhibitorsFamilial Primary Pulmonary HypertensionGlyburideHuman Umbilical Vein Endothelial CellsHumansHypertension, PulmonaryInjections, IntraperitonealMaleMAP Kinase Signaling SystemMonocrotalineNG-Nitroarginine Methyl EsterNicorandilPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRandom AllocationRatsRats, Sprague-DawleySignal TransductionVentricular PressureConceptsRight ventricular systolic pressurePulmonary arterial hypertensionHuman umbilical vein endothelial cellsVascular endothelial damageMCT injectionArterial hypertensionEndothelial damageNitro-L-arginine methyl esterNitric oxide synthase inhibitorBeneficial effectsEndothelial NOS expressionVentricular systolic pressureVehicle-treated groupChannel blocker glibenclamideOxide synthase inhibitorChannel opener nicorandilSprague-Dawley ratsCaspase-3 expressionAnti-apoptotic effectsUmbilical vein endothelial cellsPromising therapeutic potentialBcl-2 expressionAnti-apoptotic factorsNicorandil administrationVein endothelial cells
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