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
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
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 iron
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 progenitorsConcise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies
Xavier-Ferrucio J, Krause DS. Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies. Stem Cells 2018, 36: 1138-1145. PMID: 29658164, PMCID: PMC6105498, DOI: 10.1002/stem.2834.Peer-Reviewed Original ResearchConceptsMegakaryocytic-erythroid progenitorsProgenitor cellsDifferent functional outputsVariety of speciesProgenitor stageIntermediate progenitor stageErythroid cellsHuman hematopoiesisBlood formationMegakaryocytic lineageMurine cellsHematopoietic stemHematopoietic progenitorsFunctional outputStem cellsDifferentiation capabilityHematopoiesis processProgenitorsLineagesHematopoiesisCell sourceCellsDiscrete stepsRecent advancesSpecies