Featured Publications
Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation
Wang N, Zheng J, Chen Z, Liu Y, Dura B, Kwak M, Xavier-Ferrucio J, Lu YC, Zhang M, Roden C, Cheng J, Krause DS, Ding Y, Fan R, Lu J. Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation. Nature Communications 2019, 10: 95. PMID: 30626865, PMCID: PMC6327095, DOI: 10.1038/s41467-018-07981-6.Peer-Reviewed Original ResearchConceptsSame single cellMicroRNA-mRNASingle cellsGenome-scale analysisNon-genetic cellNon-genetic heterogeneityMultiple omic profilesGenomic approachesMicroRNA regulationMolecular regulationTarget mRNAsExpression variabilityCellular pathwaysRegulatory relationshipsLevels of microRNAsIntercellular heterogeneityOmics profilesIntercellular variabilityCell heterogeneityMRNA profilesMicroRNAsMRNACellsRegulationExpression
2019
MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
2015
microRNA Expression Profiling: Technologies, Insights, and Prospects
Roden C, Mastriano S, Wang N, Lu J. microRNA Expression Profiling: Technologies, Insights, and Prospects. Advances In Experimental Medicine And Biology 2015, 888: 409-421. PMID: 26663195, DOI: 10.1007/978-3-319-22671-2_21.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell Line, TumorDisease Models, AnimalGene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansMicroRNAsMolecular Sequence DataNeoplasmsReverse Transcriptase Polymerase Chain ReactionSequence Homology, Nucleic AcidSignal TransductionConceptsLong small noncoding RNAsExpression profilingMiRNA isoformsMiRNA expressionProfiling technologiesDiverse biological processesSingle-cell variabilitySmall noncoding RNAsMiRNA profiling technologiesGlobal miRNA expressionNext-generation sequencingNoncoding RNAsCell variabilitySingle-molecule measurementsBiological functionsBiological processesTumor suppressorMicroRNA researchQuantitative RT-PCRCareful experimental designMiRNAsIsoformsRT-PCRProfilingExpression
2014
A High-Throughput MicroRNA Expression Profiling System
Guo Y, Mastriano S, Lu J. A High-Throughput MicroRNA Expression Profiling System. Methods In Molecular Biology 2014, 1176: 33-44. PMID: 25030917, DOI: 10.1007/978-1-4939-0992-6_4.Peer-Reviewed Original ResearchConceptsHundreds of miRNAsSmall noncoding RNAsDiverse biological functionsMiRNA-related researchGlobal miRNA expressionTotal RNA samplesNoncoding RNAsBiological functionsHundreds of samplesMiRNA expressionRNA samplesMiRNA levelsBiochemical reactionsPathological processesRobust protocolBead-based detectionExpressionLarge numberMiRNAsMicroRNAsHigh detection specificityRNADetection specificityDeregulationHundredsNonstochastic Reprogramming from a Privileged Somatic Cell State
Guo S, Zi X, Schulz VP, Cheng J, Zhong M, Koochaki SH, Megyola CM, Pan X, Heydari K, Weissman SM, Gallagher PG, Krause DS, Fan R, Lu J. Nonstochastic Reprogramming from a Privileged Somatic Cell State. Cell 2014, 156: 649-662. PMID: 24486105, PMCID: PMC4318260, DOI: 10.1016/j.cell.2014.01.020.Peer-Reviewed Original ResearchConceptsSomatic cell stateCell statesAcquisition of pluripotencyMurine hematopoietic progenitorsEndogenous Oct4Cell cycle accelerationNonstochastic mannerSomatic cellsProgeny cellsPluripotent fateYamanaka factorsCell cycleHematopoietic progenitorsP53 knockdownPluripotencyReprogrammingCycling populationFactor expressionCellsFibroblastsImportant bottleneckKnockdownProgenitorsFateExpression
2013
C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells
Di Stefano B, Sardina JL, van Oevelen C, Collombet S, Kallin EM, Vicent GP, Lu J, Thieffry D, Beato M, Graf T. C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells. Nature 2013, 506: 235-239. PMID: 24336202, DOI: 10.1038/nature12885.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCCAAT-Enhancer-Binding Protein-alphaCell TransdifferentiationCells, CulturedCellular ReprogrammingChromatinCytosineDeoxyribonuclease IDioxygenasesDNA MethylationDNA-Binding ProteinsEpithelial-Mesenchymal TransitionInduced Pluripotent Stem CellsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceOctamer Transcription Factor-3Proto-Oncogene ProteinsProto-Oncogene Proteins c-mycSOXB1 Transcription FactorsUp-RegulationConceptsInduced pluripotent stem cellsPluripotent stem cellsTranscription factors Oct4Stem cellsTET2 enzymeChromatin accessibilityPluripotency genesRapid reprogrammingEfficient reprogrammingFactors OCT4B cell precursorsReprogrammingCell precursorsCellsB cellsGenesKLF4MYCSOX2OverexpressionEnzymeExpressionActivationAn Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant Hematopoiesis
Cheng J, Guo S, Chen S, Mastriano SJ, Liu C, D’Alessio A, Hysolli E, Guo Y, Yao H, Megyola CM, Li D, Liu J, Pan W, Roden CA, Zhou XL, Heydari K, Chen J, Park IH, Ding Y, Zhang Y, Lu J. An Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant Hematopoiesis. Cell Reports 2013, 5: 471-481. PMID: 24120864, PMCID: PMC3834864, DOI: 10.1016/j.celrep.2013.08.050.Peer-Reviewed Original ResearchConceptsKey tumor suppressorMyeloid differentiation biasTET2 expressionTranslocation 2 (TET2) geneMolecular regulationDifferentiation biasHematopoietic malignanciesTen-ElevenMalignant hematopoiesisTumor suppressorHematopoietic expansionActivity screenMiR-7MiRNAsExpression of TET2Normal hematopoiesisOncogenic potentialTET2Important pathogenic mechanismMiR-101Extensive roleMiR-29cHematopoiesisExpressionRegulation
2012
miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish
Stahlhut C, Suárez Y, Lu J, Mishima Y, Giraldez AJ. miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish. Development 2012, 139: 4356-4365. PMID: 23132244, PMCID: PMC3509730, DOI: 10.1242/dev.083774.Peer-Reviewed Original ResearchConceptsMiR-1/206Post-transcriptional modulatorsMiRNA-target interactionsMiR-1Appropriate physiological responsesRegulation of VEGFAZebrafish developmentEmbryonic developmentTarget protectorNovel functionPrecise regulationGene expressionMorphogenetic activityDevelopmental angiogenesisPutative targetsRegulate angiogenesisEssential processMiR-206Physiological responsesCellular communicationVEGFA expressionGrowth factorVascular endothelial growth factorExpressionAngiogenesisBlockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia
Jiang X, Huang H, Li Z, Li Y, Wang X, Gurbuxani S, Chen P, He C, You D, Zhang S, Wang J, Arnovitz S, Elkahloun A, Price C, Hong GM, Ren H, Kunjamma RB, Neilly MB, Matthews JM, Xu M, Larson RA, Le Beau MM, Slany RK, Liu PP, Lu J, Zhang J, He C, Chen J. Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia. Cancer Cell 2012, 22: 524-535. PMID: 23079661, PMCID: PMC3480215, DOI: 10.1016/j.ccr.2012.08.028.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell Transformation, NeoplasticDNA MethylationDown-RegulationFms-Like Tyrosine Kinase 3Gene DosageGene Expression Regulation, LeukemicHistone-Lysine N-MethyltransferaseHomeodomain ProteinsHumansLeukemiaMiceMicroRNAsMutationMyeloid Ecotropic Viral Integration Site 1 ProteinMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsNuclear ProteinsProto-Oncogene Proteins c-mycRNA-Binding ProteinsSignal TransductionConceptsMiR-150MiR-150 functionsLeukemic cell growthPathogenesis of leukemiaHoxa9/Meis1Acute leukemiaDysregulation of miRNAsExpression of microRNAsPivotal gatekeeperLeukemiaFunctional axisCell growthLeukemogenesisMYC/MLL fusion proteinsBlockadePathogenesisPosttranscriptional levelExpressionFusion proteinFLT3
2010
Lineage-Specific Transcriptional Regulation of DICER by MITF in Melanocytes
Levy C, Khaled M, Robinson KC, Veguilla RA, Chen PH, Yokoyama S, Makino E, Lu J, Larue L, Beermann F, Chin L, Bosenberg M, Song JS, Fisher DE. Lineage-Specific Transcriptional Regulation of DICER by MITF in Melanocytes. Cell 2010, 141: 994-1005. PMID: 20550935, PMCID: PMC2897150, DOI: 10.1016/j.cell.2010.05.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBcl-2-Like Protein 11Cell DifferentiationCell SurvivalCells, CulturedEpidermal CellsGene Expression RegulationGene Knockdown TechniquesHair FollicleHumansMelanocytesMembrane ProteinsMiceMice, Inbred C57BLMicrophthalmia-Associated Transcription FactorMicroRNAsPromoter Regions, GeneticProto-Oncogene ProteinsRibonuclease IIITranscription, GeneticUp-RegulationConceptsTranscriptional start siteLineage-specific transcriptional regulationDicer-dependent processingRegulatory element upstreamMITF bindsTranscriptional regulationMature miRNAsProapoptotic regulatorsMiRNA regulationStart siteMelanocyte survivalCentral regulatorDicerMelanocyte differentiationElement upstreamMiRNA expressionCell typesDicer expressionMiRNAsTranscriptional targetingMITFRegulatorMelanocytesExpressionRegulation
2008
Human multipotent stromal cells from bone marrow and microRNA: Regulation of differentiation and leukemia inhibitory factor expression
Oskowitz AZ, Lu J, Penfornis P, Ylostalo J, McBride J, Flemington EK, Prockop DJ, Pochampally R. Human multipotent stromal cells from bone marrow and microRNA: Regulation of differentiation and leukemia inhibitory factor expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 18372-18377. PMID: 19011087, PMCID: PMC2587615, DOI: 10.1073/pnas.0809807105.Peer-Reviewed Original ResearchConceptsHuman multipotent stromal cellsMultipotent stromal cellsAdipogenic differentiationRegulation of differentiationExpression of DicerStromal cellsExpression analysisHMSC differentiationEarly transcriptsFactor expressionMiRNAsLeukemia inhibitory factor expressionOsteogenic differentiationDifferentiationBone marrowExpressionDicerDroshaCellsSilico modelsMicroRNAsMiRNATranscriptsShRNAsEnzyme
2007
Altered microRNA expression in human heart disease
Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD, Golub TR, Pieske B, Pu WT. Altered microRNA expression in human heart disease. Physiological Genomics 2007, 31: 367-373. PMID: 17712037, DOI: 10.1152/physiolgenomics.00144.2007.Peer-Reviewed Original ResearchConceptsHeart diseaseDiagnostic groupsHuman heart failureLeft ventricular samplesHeart disease pathogenesisHeart failureIschemic cardiomyopathyDisease groupHeart functionDisease pathogenesisExpression profilesControl groupHuman heart diseaseVentricular samplesClinical diagnosisHuman left ventricular samplesContribution of microRNAsDiseaseFurther studiesImportant regulatorMultiple testingMiRNA expressionMicroRNAsExpressionGroup
2006
Hematopoietic gene promoters subjected to a group-combinatorial study of DNA samples: identification of a megakaryocytic selective DNA signature
Hazony Y, Lu J, St. Hilaire C, Ravid K. Hematopoietic gene promoters subjected to a group-combinatorial study of DNA samples: identification of a megakaryocytic selective DNA signature. Nucleic Acids Research 2006, 34: 4416-4428. PMID: 16936310, PMCID: PMC1636359, DOI: 10.1093/nar/gkl578.Peer-Reviewed Original ResearchConceptsCell-specific gene expressionNon-coding regionsRelated DNA sequencesDNA sequencesGene expressionMegakaryocytic lineageUnique transcription factorsCommon DNA sequenceNon-coding sequencesGroup of genesGene promoter sequencesMammalian genomesRegulatory sequencesTranscription factorsPromoter sequencesCross-species differencesGene promoterDNA signaturesLineagesSpecific sequencesCommon sequenceDNA samplesSequencePromoter groupExpression
2005
MicroRNA expression profiles classify human cancers
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 2005, 435: 834-838. PMID: 15944708, DOI: 10.1038/nature03702.Peer-Reviewed Original ResearchConceptsCluster of microRNAsHuman cancersHuman chromosome 13Non-coding RNAsImportant transcription factorMicroRNA expression profileTranscription factorsExpression profilesGlobal downregulationRegulatory moleculesDifferentiation statePotential oncogeneMiR-17C-MycChromosome 13MicroRNAsHuman B-cell lymphomasMicroRNA profilesTumor formationVivo modelRNANucleotidesOncogeneDownregulationExpression