2023
Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability
Zhang J, Wu Q, Hu X, Wang Y, Lu J, Chakraborty R, Martin K, Guo S. Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability. Stem Cells 2023, 41: 907-915. PMID: 37386941, PMCID: PMC11009695, DOI: 10.1093/stmcls/sxad051.Peer-Reviewed Original ResearchConceptsMouse pluripotent stem cellsSerum response factorPluripotent stem cellsCell fate stabilityRole of SRFGene expression noiseHeterogeneous gene expressionResponse factorStem cellsNaïve pluripotencyCell state heterogeneityLineage primingExpression noiseActin dynamicsCellular statesPluripotent cellsSRF functionCell statesMechanical signalingGene expressionFunctional modulationCentral mediatorSerum-containing culturesState heterogeneityCellsCell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling
Feng X, Sun R, Lee M, Chen X, Guo S, Geng H, Müschen M, Choi J, Pereira J. Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling. ELife 2023, 12: e83533. PMID: 36912771, PMCID: PMC10042536, DOI: 10.7554/elife.83533.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsLymphotoxin beta receptorLeukemic cellsBeta receptorsLeukemic cell growthBone marrow microenvironmentStem cellsTransplant recipientsAML cellsMyeloblastic leukemiaMouse modelBone marrowLeukemia growthLymphotoxin α1β2Marrow microenvironmentPharmacological disruptionLymphopoiesisReceptorsHematopoietic outputMolecular mechanismsErythropoiesisDNA damage response pathwayCell growthCellsPhysiological mechanisms
2022
Incorporating signaling dynamics into fate decision
Guo S. Incorporating signaling dynamics into fate decision. Blood 2022, 140: 79-80. PMID: 35834282, PMCID: PMC9283969, DOI: 10.1182/blood.2022016420.Peer-Reviewed Original Research
2020
Reprogramming progressive cells display low CAG promoter activity
Hu X, Wu Q, Zhang J, Kim J, Chen X, Hartman AA, Eastman AE, Park I, Guo S. Reprogramming progressive cells display low CAG promoter activity. Stem Cells 2020, 39: 43-54. PMID: 33075202, PMCID: PMC7821215, DOI: 10.1002/stem.3295.Peer-Reviewed Original ResearchResolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent Reporter
Eastman AE, Chen X, Hu X, Hartman AA, Morales A, Yang C, Lu J, Kueh HY, Guo S. Resolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent Reporter. Cell Reports 2020, 31: 107804. PMID: 32579930, PMCID: PMC7418154, DOI: 10.1016/j.celrep.2020.107804.Peer-Reviewed Original ResearchConceptsFluorescent reportersLive-cell fluorescent reporterCell cycle speedFluorescent timer proteinsCell proliferationCell cycle dynamicsRed fluorescent proteinFaster cycling cellsFate transitionsFusion reporterActive lociTimer proteinFluorescent proteinLength heterogeneityComplex tissuesHematopoietic cellsCycling cellsReporterFluorescence ratioCycle dynamicsProteinFunctional heterogeneityMouse strainsSolid tissuesCycle speedYAP Non-cell-autonomously Promotes Pluripotency Induction in Mouse Cells
Hartman AA, Scalf SM, Zhang J, Hu X, Chen X, Eastman AE, Yang C, Guo S. YAP Non-cell-autonomously Promotes Pluripotency Induction in Mouse Cells. Stem Cell Reports 2020, 14: 730-743. PMID: 32243844, PMCID: PMC7160372, DOI: 10.1016/j.stemcr.2020.03.006.Peer-Reviewed Original ResearchConceptsPluripotency inductionCell typesMouse somatic cellsMultiple stem cell typesHeterologous cell typesStem cell typesPluripotent stem cellsEarly embryogenesisSomatic cellsDistinct functionsMouse cellsMatricellular proteinYAPRecombinant CYR61Stem cellsAutonomous roleCyr61Specific cellsBystander cellsProteinCellsInductionPluripotencyEmbryogenesisControl mechanisms
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
2018
Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to Pluripotency
Hernandez C, Wang Z, Ramazanov B, Tang Y, Mehta S, Dambrot C, Lee YW, Tessema K, Kumar I, Astudillo M, Neubert TA, Guo S, Ivanova NB. Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to Pluripotency. Cell Stem Cell 2018, 23: 396-411.e8. PMID: 30146411, PMCID: PMC6128737, DOI: 10.1016/j.stem.2018.08.001.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsDNA damage response pathwayAcquisition of pluripotencyDamage response pathwayDNA methylation patternsStem cellsEmbryonic stem cellsESC enhancersPluripotent stem cellsMyc factorsPluripotent stateSomatic genesChromatin decompactionMolecular machineryEpigenetic remodelingEfficient reprogrammingResponse pathwaysSomatic cellsMethylation patternsPluripotencyHuman cellsEpigenomeEnhancerCellsKey role
2017
miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism
Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism. Blood 2017, 129: 1491-1502. PMID: 28053194, PMCID: PMC5356452, DOI: 10.1182/blood-2016-06-721027.Peer-Reviewed Original Research
2016
A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions
Cheng J, Roden CA, Pan W, Zhu S, Baccei A, Pan X, Jiang T, Kluger Y, Weissman SM, Guo S, Flavell RA, Ding Y, Lu J. A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions. Nature Communications 2016, 7: 11178. PMID: 27025950, PMCID: PMC4820989, DOI: 10.1038/ncomms11178.Peer-Reviewed Original ResearchAnimalsBacterial ProteinsCell LineChromosome MappingCloning, MolecularClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9DNADNA Restriction EnzymesEndonucleasesGene LibraryGenomeHumansMiceMicroRNAsOligonucleotide Array Sequence AnalysisRNA, Guide, CRISPR-Cas SystemsUntranslated Regions
2014
Nonstochastic 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
An 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-29cHematopoiesisExpressionRegulationPiwi Genes Are Dispensable for Normal Hematopoiesis in Mice
Nolde MJ, Cheng EC, Guo S, Lin H. Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice. PLOS ONE 2013, 8: e71950. PMID: 24058407, PMCID: PMC3751959, DOI: 10.1371/journal.pone.0071950.Peer-Reviewed Original ResearchConceptsPiwi genesHematopoietic stem cellsNormal adult hematopoiesisPIWI protein familyStem cellsStem/progenitor cellsDiverse organismsAdult hematopoiesisProtein familyLong-term hematopoiesisMyeloablative stressCompetitive transplantationTransient expressionHuman leukemia cell linesHSC compartmentLeukemia cell linesGenesProliferative stateNormal hematopoiesisCell typesMIWI2Progenitor cellsLineage reconstitutionHematopoiesisCell proliferationDynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging
Megyola CM, Gao Y, Teixeira AM, Cheng J, Heydari K, Cheng E, Nottoli T, Krause DS, Lu J, Guo S. Dynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging. Stem Cells 2013, 31: 895-905. PMID: 23335078, PMCID: PMC4309553, DOI: 10.1002/stem.1323.Peer-Reviewed Original ResearchConceptsCell-cell interactionsEarly reprogrammingDynamic cell-cell interactionsSingle-cell resolutionTime-lapse microscopyE-cadherin inhibitionTime-lapse imagingPluripotency inductionInduced pluripotencyGranulocyte-monocyte progenitorsPluripotent cellsReprogrammingMolecular mechanismsCell resolutionCell migrationCellular interactionsGenetic makeupE-cadherinSatellite coloniesExperimental systemHematopoietic stateSource cellsRare cellsColoniesComplex mechanisms
2012
An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response
Adams BD, Guo S, Bai H, Guo Y, Megyola CM, Cheng J, Heydari K, Xiao C, Reddy EP, Lu J. An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response. Cell Reports 2012, 2: 1048-1060. PMID: 23084747, PMCID: PMC3487471, DOI: 10.1016/j.celrep.2012.09.014.Peer-Reviewed Original ResearchConceptsMiR-150Injury responseBone marrow transplant modelCareful clinical managementHematopoietic suppressionTransplant modelPeripheral bloodHematopoietic recoveryRecipient miceClinical managementAssociated impairmentRole of microRNAsMyeloid cellsHeterozygous knockoutProgenitor cellsClonogenic potentialMajor blood lineagesNormal tissue physiologyHematopoietic stemTissue physiologyC-MybTreatmentMicroRNAsFunction screenCellsComplex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms
Guo S, Bai H, Megyola CM, Halene S, Krause DS, Scadden DT, Lu J. Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16636-16641. PMID: 23012470, PMCID: PMC3478612, DOI: 10.1073/pnas.1213196109.Peer-Reviewed Original ResearchAnimalsBone Marrow CellsBone Marrow NeoplasmsBone Marrow TransplantationCell LineColony-Forming Units AssayDoxycyclineFlow CytometryGene Expression Regulation, NeoplasticGranulocyte-Macrophage Colony-Stimulating FactorInterleukin-3Leukocytes, MononuclearMiceMice, Inbred C57BLMicroRNAsMyeloproliferative DisordersOncogenesReverse Transcriptase Polymerase Chain Reaction
2010
A microRNA regulating adult hematopoietic stem cells
Guo S, Scadden DT. A microRNA regulating adult hematopoietic stem cells. Cell Cycle 2010, 9: 3637-3638. PMID: 20855952, DOI: 10.4161/cc.9.18.13174.Peer-Reviewed Original ResearchMicroRNA miR-125a controls hematopoietic stem cell number
Guo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, Purton LE, Fleming HH, Cobb B, Merkenschlager M, Golub TR, Scadden DT. MicroRNA miR-125a controls hematopoietic stem cell number. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 14229-14234. PMID: 20616003, PMCID: PMC2922532, DOI: 10.1073/pnas.0913574107.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsStem cell pool sizeStem cell stateLong-term hematopoietic stem cellsCell-autonomous mannerStem cellsStem cell populationCell pool sizeMiR-125aStem cell numbersHematopoietic stem cell numbersEnzyme DicerImmature hematopoietic progenitorsHematopoietic differentiationMutant animalsCell statesProgenitor cell apoptosisMicroRNA processing enzyme DicerMicroRNA clusterProapoptotic genesHSPC populationsHematopoietic expansionSpecific microRNAsUnique microRNAsHSPC apoptosisBone progenitor dysfunction induces myelodysplasia and secondary leukaemia
Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 2010, 464: 852-857. PMID: 20305640, PMCID: PMC3422863, DOI: 10.1038/nature08851.Peer-Reviewed Original ResearchConceptsSpecific mesenchymal cellsMesenchymal cellsHuman bone marrow failureDeletion of Dicer1Osteolineage cellsTissue homeostasisHeterologous cellsDicer1 deletionGene expressionMature osteoblastsRegulatory nicheBone marrow failureDiamond syndromeMesenchymal subsetsStem cellsOsteoprogenitorsReduced expressionDeletionSecondary neoplastic diseaseStromal cellsMarrow failureDICER1CellsHaematopoiesisGenetic abnormalities
2008
MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors
Lu J, Guo S, Ebert BL, Zhang H, Peng X, Bosco J, Pretz J, Schlanger R, Wang JY, Mak RH, Dombkowski DM, Preffer FI, Scadden DT, Golub TR. MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors. Developmental Cell 2008, 14: 843-853. PMID: 18539114, PMCID: PMC2688789, DOI: 10.1016/j.devcel.2008.03.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD34Bone Marrow CellsCell DifferentiationCell LineageCells, CulturedErythroid CellsErythropoietinGene Expression RegulationGenes, ReporterHematopoietic Stem CellsHumansIntegrin beta3K562 CellsMegakaryocytesMiceMice, Inbred C57BLMicroRNAsModels, BiologicalPlatelet Membrane Glycoprotein IIbProto-Oncogene Proteins c-mybThrombopoietinConceptsMegakaryocyte-erythrocyte progenitorsLineage specificationTranscription factor MYBMiR-150Cell fateLineage fateRegenerative biologyErythroid cellsFunction experimentsMultipotent cellsMegakaryocytic lineageMiRNA expressionPrimary cellsCritical targetModel systemMicroRNAsProgenitorsFateRegulationCellsImportant participantsMYBLineagesMiRNAsBiology