2018
In utero nanoparticle delivery for site-specific genome editing
Ricciardi AS, Bahal R, Farrelly JS, Quijano E, Bianchi AH, Luks VL, Putman R, López-Giráldez F, Coşkun S, Song E, Liu Y, Hsieh WC, Ly DH, Stitelman DH, Glazer PM, Saltzman WM. In utero nanoparticle delivery for site-specific genome editing. Nature Communications 2018, 9: 2481. PMID: 29946143, PMCID: PMC6018676, DOI: 10.1038/s41467-018-04894-2.Peer-Reviewed Original ResearchConceptsSite-specific genome editingReversal of splenomegalyPeptide nucleic acidIntra-amniotic administrationBlood hemoglobin levelsMonogenic disordersNanoparticle deliveryPolymeric nanoparticlesPostnatal elevationGestational ageHemoglobin levelsImproved survivalPediatric morbidityDisease improvementHuman β-thalassemiaReticulocyte countNormal organ developmentMouse modelNormal rangeEarly interventionGenome editingOff-target mutationsPostnatal growthGene editingVersatile method
2016
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L, Qin L, Tellides G, Hirschi K, Meadows J, Soufer R, Chun HJ, Sadeghi M, Bender JR, Morrison AR. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production. Arteriosclerosis Thrombosis And Vascular Biology 2016, 37: 328-340. PMID: 27834690, PMCID: PMC5269510, DOI: 10.1161/atvbaha.116.308507.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedCoronary Artery DiseaseCoronary VesselsFemaleGenetic Predisposition to DiseaseHumansInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMacrophagesMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropeptidesPhenotypePlaque, AtheroscleroticPrognosisRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSignal TransductionTransfectionUp-RegulationVascular CalcificationConceptsCoronary calcium burdenIL-1β expressionCalcium burdenSerum IL-1β levelsElevated IL-1βIL-1β levelsCoronary artery diseaseInterleukin-1β expressionCalcified coronary arteryCardiovascular deathCardiovascular eventsArtery diseaseIndependent predictorsClinical outcomesVascular calcificationCoronary arteryIL-1βPlaque calciumAtherosclerotic calcificationExperimental atherogenesisInflammatory regulatorsMacrophage interleukinAtherosclerotic plaquesTherapeutic targetProgressive calcification
2014
Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells
Coşkun S, Chao H, Vasavada H, Heydari K, Gonzales N, Zhou X, de Crombrugghe B, Hirschi KK. Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells. Cell Reports 2014, 9: 581-590. PMID: 25310984, PMCID: PMC4266564, DOI: 10.1016/j.celrep.2014.09.013.Peer-Reviewed Original ResearchConceptsOsteolineage cellsHematopoietic stem cellsHSC developmentCellular componentsAdult-repopulating hematopoietic stem cellsBone marrow nicheEmbryonic day 16.5HSC quiescenceMultilineage progenitorsSpecialized nichesNiche formationFetal bone marrow cellsHSC activityMarrow nicheMultilineage coloniesStem cellsBone marrow cellsDay 16.5NicheHSC proliferationHoming abilityMarrow cellsCellsBone marrowStromal components
2013
Hemogenic Endothelial Cell Specification Requires c-Kit, Notch Signaling, and p27-Mediated Cell-Cycle Control
Marcelo KL, Sills TM, Coskun S, Vasavada H, Sanglikar S, Goldie LC, Hirschi KK. Hemogenic Endothelial Cell Specification Requires c-Kit, Notch Signaling, and p27-Mediated Cell-Cycle Control. Developmental Cell 2013, 27: 504-515. PMID: 24331925, PMCID: PMC3994666, DOI: 10.1016/j.devcel.2013.11.004.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde OxidoreductasesAnimalsAntineoplastic AgentsCell Cycle CheckpointsCell DifferentiationCore Binding Factor Alpha 2 SubunitCyclin-Dependent Kinase Inhibitor p27Embryo Culture TechniquesEndothelial CellsFemaleHematopoietic Stem CellsLac OperonLentivirusMaleMiceMice, KnockoutPregnancyProto-Oncogene Proteins c-kitProto-Oncogene Proteins c-mybReceptor, Notch1Signal TransductionTretinoinConceptsCell cycle controlEndothelial cell specificationEndothelial cell developmentNotch signalingCell specificationCell developmentPrimordial endothelial cellsHemogenic endothelial cellsRetinoic acidCell cycle regulationC-kitHuman stem cellsRas regulationEndothelial cellsMolecular signalsStem cellsSignalingP27 expressionP27RegulationCellsEmbryogenesisClinical therapyMechanismExpression
2011
The Transcription Factor E74-Like Factor Controls Quiescence of Endothelial Cells and Their Resistance to Myeloablative Treatments in Bone Marrow
Sivina M, Yamada T, Park CS, Puppi M, Coskun S, Hirschi K, Lacorazza HD. The Transcription Factor E74-Like Factor Controls Quiescence of Endothelial Cells and Their Resistance to Myeloablative Treatments in Bone Marrow. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 1185-1191. PMID: 21350194, PMCID: PMC3100289, DOI: 10.1161/atvbaha.111.224436.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell CycleCell ProliferationCellular SenescenceChlorocebus aethiopsCOS CellsCyclin-Dependent Kinase 4DNA-Binding ProteinsDrug ResistanceEndothelial CellsFluorouracilHumansMiceMice, Inbred C57BLMice, KnockoutMyeloablative AgonistsNeovascularization, PhysiologicNIH 3T3 CellsPromoter Regions, GeneticRNA InterferenceTime FactorsTranscription FactorsTransfectionConceptsBone marrowEndothelial cellsSinusoidal blood vesselsCyclin-dependent kinase 4 expressionBlood vesselsCyclin-dependent kinase 4Human umbilical vein endothelial cellsBone marrow endothelial cellsUmbilical vein endothelial cellsMurine endothelial cellsMarrow endothelial cellsVein endothelial cellsMyeloablative treatmentCD45- CD31Cell cycle entryProgenitor cellsMarrowKinase 4Hematopoietic systemCycle entryVascular networkCellsProliferationLineage-specific progenitor cellsVessels
2010
Establishment and regulation of the HSC niche: Roles of osteoblastic and vascular compartments
Coskun S, Hirschi KK. Establishment and regulation of the HSC niche: Roles of osteoblastic and vascular compartments. Birth Defects Research Part C Embryo Today Reviews 2010, 90: 229-242. PMID: 21181885, PMCID: PMC5226239, DOI: 10.1002/bdrc.20194.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsAdult bone marrow nichesExtraembryonic yolk sacVascular endothelial cellsAdult bone marrowBone marrow nicheMammalian embryogenesisHSC formationBlood cell typesHematopoiesis changeAorta-gonadHSC generationMesonephros (AGM) regionHSC maturationMajor regulatory factorLifelong supplyMajor cellular componentHSC nicheEndothelial cellsMulti-potent cellsRegulatory factorsCellular componentsCell typesMarrow nicheDifferent tissuesMdm2 Is Required for Survival of Hematopoietic Stem Cells/Progenitors via Dampening of ROS-Induced p53 Activity
Abbas HA, Maccio DR, Coskun S, Jackson JG, Hazen AL, Sills TM, You MJ, Hirschi KK, Lozano G. Mdm2 Is Required for Survival of Hematopoietic Stem Cells/Progenitors via Dampening of ROS-Induced p53 Activity. Cell Stem Cell 2010, 7: 606-617. PMID: 21040902, PMCID: PMC3026610, DOI: 10.1016/j.stem.2010.09.013.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesPostnatal day 13Cell cycle arrestAbsence of Mdm2Bone marrowAntioxidant treatmentStem cells/progenitorsDay 13Hematopoietic stem cellsMicePostnatal bone marrowFetal liverHematopoietic failureCycle arrestHematopoietic compartmentP53 levelsHematopoietic cellsP53 activityCell deathStem cellsMDM2Survival