Featured Publications
Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation
Scanlon VM, Thompson EN, Lawton BR, Kochugaeva M, Ta K, Mayday MY, Xavier-Ferrucio J, Kang E, Eskow NM, Lu YC, Kwon N, Laumas A, Cenci M, Lawrence K, Barden K, Larsuel ST, Reed FE, Peña-Carmona G, Ubbelohde A, Lee JP, Boobalan S, Oppong Y, Anderson R, Maynard C, Sahirul K, Lajeune C, Ivathraya V, Addy T, Sanchez P, Holbrook C, Van Ho AT, Duncan JS, Blau HM, Levchenko A, Krause DS. Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation. Scientific Reports 2022, 12: 16218. PMID: 36171423, PMCID: PMC9519589, DOI: 10.1038/s41598-022-19013-x.Peer-Reviewed Original ResearchConceptsMegakaryocytic-erythroid progenitorsFate specificationLineage commitmentUnderstanding of hematopoiesisProgenitor cell biologyPrimary human hematopoietic progenitorsSingle-cell trackingSingle-cell assaysSingle-cell levelHuman hematopoietic progenitorsProgenitor cell dynamicsLineage specificationCell fateColony-forming unit assaysTimelapse imagingSitu fluorescence stainingCell biologyLineage tracingDivision rateCytokine thrombopoietinHematopoietic progenitorsProgenitorsFluorescence stainingCell dynamicsUnit assays
2024
3109 – OPTIMIZING AND SIMPLIFYING READOUT OF HEMATOPOIETIC COLONY FORMING UNIT (CFU) ASSAYS
Krause D, Thompson E, Carlino M, Scanlon V. 3109 – OPTIMIZING AND SIMPLIFYING READOUT OF HEMATOPOIETIC COLONY FORMING UNIT (CFU) ASSAYS. Experimental Hematology 2024, 137: 104431. DOI: 10.1016/j.exphem.2024.104431.Peer-Reviewed Original ResearchColony forming unitsCell typesProportion of coloniesFluorescence activated cell sortingColony morphologyForming unitsColony typesIdentification of basophilsLineagesColony forming unit assayCell morphologyCell sortingColoniesIndividual stemsSemisolid mediumMK cellsMultipotent progenitorsDetect GProgenitor populationsLineage potentialCommon myeloid progenitorsCellsIL-3Megakaryocytic lineageCombination of G-CSF
2023
Assay optimization for the objective quantification of human multilineage colony-forming units
Thompson E, Carlino M, Scanlon V, Grimes H, Krause D. Assay optimization for the objective quantification of human multilineage colony-forming units. Experimental Hematology 2023, 124: 36-44.e3. PMID: 37271449, PMCID: PMC10527702, DOI: 10.1016/j.exphem.2023.05.007.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingLineage potentialCommon myeloid progenitorsHigh-throughput microscopyMultilineage colony-forming unitsProportion of coloniesSpecific growth factorsCFU assayColony-forming unit assaysMultipotent progenitorsProgenitor populationsLineage outputSitu immunofluorescenceMegakaryocytic lineageMK cellsMegakaryocytic cellsCell typesMyeloid progenitorsProgenitor cellsCell morphologyCell sortingUnit assaysIL-3Colony typesCulture conditionsSATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction
Wilkes M, Chae H, Scanlon V, Cepika A, Wentworth E, Saxena M, Eskin A, Chen Z, Glader B, Roncarolo M, Nelson S, Sakamoto K. SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction. Stem Cells 2023, 41: 560-569. PMID: 36987811, PMCID: PMC10267687, DOI: 10.1093/stmcls/sxad025.Peer-Reviewed Original ResearchConceptsMegakaryocyte/erythroid progenitorsSpecial AT-rich sequence-binding protein 1Diamond-Blackfan anemiaInherited bone marrow failure syndromeChromatin loopsInduction of HSP70Hsp70 geneShock protein 70Progenitor expansionBiological functionsEarly myeloid progenitorsBone marrow failure syndromesErythroid factorsErythroid progenitorsMyeloid progenitorsMarrow failure syndromesProtein 1Protein 70Blackfan anemiaHSP70Specific sitesProgenitorsCell modelSATB1 expressionInduction
2022
Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization
Reed F, Eskow N, Min E, Carlino M, Mancuso R, Kwon N, Smith E, Larsuel S, Wang L, Scanlon V, Krause D. Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization. Haematologica 2022, 107: 2972-2976. PMID: 36453520, PMCID: PMC9713552, DOI: 10.3324/haematol.2021.280499.Peer-Reviewed Original ResearchStructure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization.
Reed FE, Eskow NM, Min E, Carlino M, Mancuso R, Kwon N, Smith EC, Larsuel ST, Wang L, Scanlon V, Krause DS. Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization. Haematologica 2022 PMID: 36005559.Peer-Reviewed Original ResearchDownregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond–Blackfan anemia
Wilkes MC, Scanlon V, Shibuya A, Cepika AM, Eskin A, Chen Z, Narla A, Glader B, Roncarolo MG, Nelson SF, Sakamoto KM. Downregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond–Blackfan anemia. Experimental Hematology 2022, 111: 66-78. PMID: 35460833, PMCID: PMC9255422, DOI: 10.1016/j.exphem.2022.04.005.Peer-Reviewed Original ResearchConceptsMegakaryocyte/erythroid progenitorsDiamond-Blackfan anemiaRibosomal proteinsPathogenesis of DBAErythroid progenitorsHuman hematopoietic stemInherited bone marrow failure syndromeChromatin regulatorsRibosomal insufficiencyErythroid differentiationProgenitor expansionBone marrow failure syndromesCancer predispositionHematopoietic stemMiR-30MiR-34Molecular pathwaysMegakaryocyte expansionMarrow failure syndromesNormal erythropoiesisProgenitor cellsCoordinated actionSATB1ProgenitorsDifferentiation
2021
SATB1 Regulates Chromatin Organization and HSP70 Expression in Early Erythropoiesis and Is Downregulated in Models of Diamond Blackfan Anemia
Wilkes M, Shibuya A, Scanlon V, Chae H, Narla A, Sakamoto K. SATB1 Regulates Chromatin Organization and HSP70 Expression in Early Erythropoiesis and Is Downregulated in Models of Diamond Blackfan Anemia. Blood 2021, 138: 2189. DOI: 10.1182/blood-2021-153814.Peer-Reviewed Original ResearchDiamond-Blackfan anemiaInduction of HSP70Early erythropoiesisHsp70 geneErythroid transcription factor GATA1Ribosomal protein RPS19Transcription factor GATA1Blackfan anemiaBulk RNA-seqCritical molecular mechanismsCord blood HSPCsChromatin organizationChromatin loopsRibosomal genesHematopoietic stem cellsRNA-seqSpecial ATUncommitted progenitorsErythroid differentiationProgenitor expansionProximal promoterErythroid defectsMolecular mechanismsRare genetic diseaseAnemia phenotypeSingle-Cell Tracking By Time Lapse Imaging Confirms Thrombopoietin Promotes Megakaryocytic-Erythroid Progenitor Self Renewal, but Does Not Instruct Lineage Commitment
Scanlon V, Kochugaeva M, Lawton B, Xavier-Ferrucio J, Kang E, Eskow N, Lu Y, Kwon N, Laumas A, Cenci M, Lawrence K, Barden K, Larsuel S, Reed F, Pena-Carmona G, Ubbelohde A, Lee J, Boobalan S, Oppong Y, Anderson R, Maynard C, Sahirul K, Lajeune C, Ivathraya V, Addy T, Sanchez P, Holbrook C, Van Ho A, Blau H, Levchenko A, Krause D. Single-Cell Tracking By Time Lapse Imaging Confirms Thrombopoietin Promotes Megakaryocytic-Erythroid Progenitor Self Renewal, but Does Not Instruct Lineage Commitment. Blood 2021, 138: 3270. DOI: 10.1182/blood-2021-154360.Peer-Reviewed Original ResearchAbsence of thrombopoietinTime-lapse imagingLineage commitmentSelf-renewal divisionsCell typesMK lineageSelf-RenewalLineage-restricted progenitor cellsSpecific progenitor populationsProgenitor self-renewalProgenitor cellsSingle-cell trackingSpecific cell typesColony typesE lineageLineage choiceProgenitor commitmentCellular processesDaughter cellsLineage potentialCultured megakaryocytesProgenitor populationsCell statesDivision rateMegakaryocytic maturationMRTFA: A critical protein in normal and malignant hematopoiesis and beyond
Reed F, Larsuel ST, Mayday MY, Scanlon V, Krause DS. MRTFA: A critical protein in normal and malignant hematopoiesis and beyond. Journal Of Biological Chemistry 2021, 296: 100543. PMID: 33722605, PMCID: PMC8079280, DOI: 10.1016/j.jbc.2021.100543.Peer-Reviewed Original ResearchConceptsMalignant hematopoiesisActin cytoskeleton dynamicsCritical cellular functionsResponse factorSerum response factorTranscription factor ACellular rolesImmediate early genesProtein partnersTranscriptional regulationCytoskeleton dynamicsCellular functionsTranscriptional targetsTranscription factorsCytoskeletal proteinsCritical proteinsMRTFAEarly genesCell typesChromosomal translocationsHematopoietic cellsCell growthFactor AHematopoiesisMuscle cells
2020
Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants.
Kwon N, Thompson EN, Mayday MY, Scanlon V, Lu YC, Krause DS. Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants. Current Opinion In Hematology 2020, 28: 28-35. PMID: 33186151, PMCID: PMC7737300, DOI: 10.1097/moh.0000000000000625.Peer-Reviewed Original ResearchConceptsMegakaryocyte-erythroid progenitorsFate decisionsCell fate decisionsMegakaryocytic-erythroid progenitorsGene expression patternsProgenitor cell biologyFate determinantsFate determinationCurrent understandingTranscription factorsCell biologyExpression patternsPluripotent progenitorsProgenitorsModel systemExtrinsic factorsBiologyDisease statesFateDevelopment leadEpigeneticsMegakaryocytesUnderstandingDiscoveryIsolation
2019
Low iron promotes megakaryocytic commitment of megakaryocytic-erythroid progenitors in humans and mice
Xavier-Ferrucio J, Scanlon V, Li X, Zhang PX, Lozovatsky L, Ayala-Lopez N, Tebaldi T, Halene S, Cao C, Fleming MD, Finberg KE, Krause DS. Low iron promotes megakaryocytic commitment of megakaryocytic-erythroid progenitors in humans and mice. Blood 2019, 134: 1547-1557. PMID: 31439541, PMCID: PMC6839952, DOI: 10.1182/blood.2019002039.Peer-Reviewed Original ResearchConceptsMK lineage commitmentExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwayMegakaryocytic-erythroid progenitorsBone marrow transplantation assaysSignal transduction analysisIron-deficient conditionsGene expression analysisMegakaryocytic commitmentLineage commitmentTransferrin receptor 2MK lineageTmprss6-/- miceIron sensorExpression analysisKinase pathwayTransduction analysisTransplantation assaysErythroid progenitorsMarrow environmentHematopoietic cellsMessenger RNAPhospho-ERK1/2Systemic iron deficiencyLow ironEpithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability
Scanlon VM, Teixeira AM, Tyagi T, Zou S, Zhang PX, Booth CJ, Kowalska MA, Bao J, Hwa J, Hayes V, Marks MS, Poncz M, Krause DS. Epithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability. Thrombosis And Haemostasis 2019, 119: 744-757. PMID: 30861547, PMCID: PMC6599679, DOI: 10.1055/s-0039-1679908.Peer-Reviewed Original ResearchConceptsConditional knockout miceKnockout micePlatelet aggregationE-cadherinClot stabilityClot stabilizationSynthase kinase 3β activationAntibody-mediated platelet depletionVivo injury modelsNull plateletsPlatelet productionWild-type miceTail bleeding timeAkt/GSK3βMurine platelet aggregationKnockout mouse modelPlatelet dysfunctionFibrin depositionInjury modelPlatelet depletionPrimary human plateletsBleeding timeMouse modelPlatelet numberE-cadherin antibody
2016
Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation
Scanlon V, Walia B, Yu J, Hansen M, Drissi H, Maye P, Sanjay A. Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation. Bone 2016, 95: 124-135. PMID: 27884787, PMCID: PMC5819877, DOI: 10.1016/j.bone.2016.11.020.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsBiomarkersCell CountCell DifferentiationCell LineageCell NucleusCell ProliferationFracture HealingFractures, BoneMesodermMice, Inbred C57BLMutationOsteogenesisPeriosteumPhosphatidylinositol 3-KinasePhosphorylationProtein BindingProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-cblSp7 Transcription FactorUp-RegulationConceptsCbl-PI3K interactionUbiquitin ligase functionMultipotent skeletal progenitorsPeriosteal cellsPI3KMajor adaptor proteinP85 regulatory subunitTranscriptional target genesE3 ubiquitin ligaseOsteogenic differentiationPhosphatidylinositol-3 kinasePI3K regulationMajor signaling proteinsK interactionPI3K activityPeriosteal thickeningLipid kinasesP85 subunitSkeletal progenitorsAdaptor proteinRegulatory subunitLigase functionSignaling proteinsUbiquitin ligaseNuclear localizationIncreased periosteal expansion, Osterix expression and osteogenic potential upon bone injury during perturbed PI3K signaling
Walia B, Scanlon V, Yu J, Maye P, Drissi H, Sanjay A. Increased periosteal expansion, Osterix expression and osteogenic potential upon bone injury during perturbed PI3K signaling. Bone Abstracts 2016 DOI: 10.1530/boneabs.5.p75.Peer-Reviewed Original Research
2015
Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair
Scanlon V, Soung do Y, Adapala NS, Morgan E, Hansen MF, Drissi H, Sanjay A. Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair. PLOS ONE 2015, 10: e0138194. PMID: 26393915, PMCID: PMC4578922, DOI: 10.1371/journal.pone.0138194.Peer-Reviewed Original ResearchConceptsCbl-PI3K interactionHistomorphometric analysisFracture callusBone formationMid-diaphyseal femoral fracturePI3KNormal bone homeostasisBony callus formationSoft callus formationHealing femursFemoral fracturesWT miceOsteoclast numberBone resorptionTomography scanMurine modelOsteoblast surfaceFracture healingBone homeostasisBone volumeBone repairSkeletal remodelingMiceBiomechanical testingHigh expression
2014
Loss of Cbl–PI3K interaction in mice prevents significant bone loss following ovariectomy
Adapala NS, Holland D, Scanlon V, Barbe MF, Langdon WY, Tsygankov AY, Lorenzo JA, Sanjay A. Loss of Cbl–PI3K interaction in mice prevents significant bone loss following ovariectomy. Bone 2014, 67: 1-9. PMID: 24994594, PMCID: PMC4149851, DOI: 10.1016/j.bone.2014.06.013.Peer-Reviewed Original ResearchConceptsCbl-PI3K interactionSignificant bone lossBone lossSerum levelsBone resorptionBone remodelingPro-collagen type 1Bone resorbing activityDefective bone resorptionC-terminal telopeptideP1NP levelsSerum CTXResorbing activityL2 vertebraBone volumeOvariectomyTyrosine 737Mice resultsType 1Lumbar vertebraeMiceBone formationOsteoclast migrationBone developmentResorptionEstablishment of Human cell Type-Specific iPS cells with Enhanced Chondrogenic Potential
Guzzo RM, Scanlon V, Sanjay A, Xu RH, Drissi H. Establishment of Human cell Type-Specific iPS cells with Enhanced Chondrogenic Potential. Stem Cell Reviews And Reports 2014, 10: 820-829. PMID: 24958240, DOI: 10.1007/s12015-014-9538-8.Peer-Reviewed Original ResearchConceptsIPS cellsCell typesVivo functional analysisSpecialized cell typesNew cellular toolsSomatic cell typesChondrogenic potentialDelivery of Oct4Pluripotent differentiation capacityCell linesPluripotent stem cellsArticular chondrocytesHuman articular chondrocytesFate potentialEnhanced chondrogenic potentialHigh chondrogenic potentialSpecific lineagesFibroblast cell lineTissue of originCellular toolsGene expressionFunctional analysisDermal fibroblast cell lineChondrogenic differentiationDifferentiation capacity
2012
Retroelement demethylation associated with abnormal placentation in Mus musculus x Mus caroli hybrids.
Brown JD, Piccuillo V, O'Neill RJ. Retroelement demethylation associated with abnormal placentation in Mus musculus x Mus caroli hybrids. Biology Of Reproduction 2012, 86: 88. PMID: 22116807, DOI: 10.1095/biolreprod.111.095273.Peer-Reviewed Original Research