2024
CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors
Kwon N, Lu Y, Thompson E, Mancuso R, Wang L, Zhang P, Krause D. CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors. Blood 2024, 144: 1800-1812. PMID: 39102635, PMCID: PMC11530366, DOI: 10.1182/blood.2024023963.Peer-Reviewed Original ResearchMegakaryocytic-erythroid progenitorsWild-typeFate specificationRUNX1 levelsCell lines expressing wild-typeHuman erythroleukemiaInhibition of CDK9Cell-type specific transcription factorsMK-specificRUNX1 variantsDifferentially regulates expressionErythroid commitmentHematopoietic homeostasisHuman erythroleukemia cellsMK progenitorsOverexpression of RUNX1Megakaryocyte fateDecreased expressionRUNX1Mimetic mutationNon-phosphorylatableTranscription machineryFunctional efficacySerine/threonine phosphorylationSerine/threonine kinase
2023
3092 – CRISPR OPTIMIZATION TO SCREEN FOR GENES THAT REGULATE FATE SPECIFICATION OF PRIMARY HUMAN HEMATOPOIETIC PROGENITORS
Mancuso R, Thompson E, Wang L, Krause D. 3092 – CRISPR OPTIMIZATION TO SCREEN FOR GENES THAT REGULATE FATE SPECIFICATION OF PRIMARY HUMAN HEMATOPOIETIC PROGENITORS. Experimental Hematology 2023, 124: s96. DOI: 10.1016/j.exphem.2023.06.199.Peer-Reviewed Original ResearchFate specificationMCherry fluorescent reporterFluorescent reportersNumber of genesLarge-scale screenDNA-PK inhibitorPrimary human hematopoietic progenitorsHuman hematopoietic progenitorsCD45-negative cellsPanel of genesCRISPR screensErythroid maturationSingle guideMolecular mechanismsGRNAGRNA sequencesNegative cellsGenesHematopoietic progenitorsLentiviral transductionTotal RNAReporterProgenitorsTransfectionCell number3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION
Kwon N, Lu Y, Thompson E, Wang L, Zhang P, Krause D. 3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION. Experimental Hematology 2023, 124: s104. DOI: 10.1016/j.exphem.2023.06.215.Peer-Reviewed Original ResearchMegakaryocyte-erythroid progenitorsFate specificationHEL cellsGene expressionSingle-cell RNA-seq dataPost-translational modificationsDifferential gene expressionRNA-seq dataChromatin localizationRNA-seqPhosphorylation statusRUNX1 overexpressionE progenitorsTranscriptional activityKey regulatorRUNX1 mRNAMK progenitorsT residuesGenesErythroid progenitorsRUNX1MKPProgenitorsProtein levelsSpecification mechanism
2022
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
2018
The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification
Lu YC, Sanada C, Xavier-Ferrucio J, Wang L, Zhang PX, Grimes HL, Venkatasubramanian M, Chetal K, Aronow B, Salomonis N, Krause DS. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell Reports 2018, 25: 2083-2093.e4. PMID: 30463007, PMCID: PMC6336197, DOI: 10.1016/j.celrep.2018.10.084.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell CycleCell LineageGene Expression RegulationGene Regulatory NetworksHEK293 CellsHigh-Throughput Nucleotide SequencingHumansMegakaryocyte-Erythroid Progenitor CellsProto-Oncogene Proteins c-mycReproducibility of ResultsSignal TransductionTranscription, GeneticTumor Suppressor Protein p53ConceptsMegakaryocytic-erythroid progenitorsCommon myeloid progenitorsTranscription factorsCell cycleSingle-cell RNA sequencingRegulatory transcription factorsMegakaryocyte-erythroid progenitorsCell cycle regulatorsCell cycle activationFate specificationLineage specificationE lineageMalignant disease statesGenetic manipulationRNA sequencingE progenitorsErythroid maturationCycle regulatorsDifferential expressionHuman cellsHealthy human cellsCycle activationMegakaryocyte progenitorsMolecular signaturesMyeloid progenitors