2015
DNMT3A in haematological malignancies
Yang L, Rau R, Goodell M. DNMT3A in haematological malignancies. Nature Reviews Cancer 2015, 15: 152-165. PMID: 25693834, PMCID: PMC5814392, DOI: 10.1038/nrc3895.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHaematopoietic stem cell differentiationStem cell differentiationStem cell programAberrant DNA methylationDominant negative inhibitorImportant biological relationshipsDifferentiated lineagesHistone methyltransferasesDNA methyltransferasesRegulatory domainDNA methylationMechanistic functionGene expressionHSC progenyMethyltransferase 3AImportant new targetHSC expansionCell differentiationUnique mutational profileDNMT3ACell programHuman HSCsStem cellsEnzymatic activityMutationsDnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation
Mayle A, Yang L, Rodriguez B, Zhou T, Chang E, Curry C, Challen G, Li W, Wheeler D, Rebel V, Goodell M. Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation. Blood 2015, 125: 629-638. PMID: 25416277, PMCID: PMC4304108, DOI: 10.1182/blood-2014-08-594648.Peer-Reviewed Original ResearchConceptsHematologic malignanciesDNMT3A mutationsB-cell acute lymphocytic leukemiaAcute lymphocytic leukemiaSpectrum of malignanciesAcute myeloid leukemiaStem cellsPreleukemic phenotypeMyelodysplastic syndromePoor prognosisMyeloid leukemiaLymphocytic leukemiaLymphoid malignanciesMouse modelIrradiated micePrimary myelofibrosisMalignancyPreleukemic cellsLoss of functionDNA methyltransferase 3AMalignant transformationHematopoietic stem cellsMyeloid diseasesLeukemiaLymphoid lineage
2014
Dnmt3a and Dnmt3b Have Overlapping and Distinct Functions in Hematopoietic Stem Cells
Challen G, Sun D, Mayle A, Jeong M, Luo M, Rodriguez B, Mallaney C, Celik H, Yang L, Xia Z, Cullen S, Berg J, Zheng Y, Darlington G, Li W, Goodell M. Dnmt3a and Dnmt3b Have Overlapping and Distinct Functions in Hematopoietic Stem Cells. Cell Stem Cell 2014, 15: 350-364. PMID: 25130491, PMCID: PMC4163922, DOI: 10.1016/j.stem.2014.06.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBeta CateninCell DifferentiationCell ProliferationCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEpigenesis, GeneticGene Expression Regulation, DevelopmentalGene Regulatory NetworksHematopoietic Stem CellsIsoenzymesMice, Inbred C57BLMice, KnockoutNeoplasmsConceptsHematopoietic stem cellsDe novo methylation patternsAdult hematopoietic stem cellsHSC fate decisionsLoss of Dnmt3bStem cellsΒ-catenin signalingFate decisionsEpigenetic regulationMethylation patternsCpG islandsLifelong productionDistinct functionsHSC differentiationConditional inactivationDNMT3BHSC expansionDifferentiation blockSevere blockDistinct rolesImpaired differentiationDifferentiationMild phenotypeRegulationCells
2013
Large conserved domains of low DNA methylation maintained by Dnmt3a
Jeong M, Sun D, Luo M, Huang Y, Challen G, Rodriguez B, Zhang X, Chavez L, Wang H, Hannah R, Kim S, Yang L, Ko M, Chen R, Göttgens B, Lee J, Gunaratne P, Godley L, Darlington G, Rao A, Li W, Goodell M. Large conserved domains of low DNA methylation maintained by Dnmt3a. Nature Genetics 2013, 46: 17-23. PMID: 24270360, PMCID: PMC3920905, DOI: 10.1038/ng.2836.Peer-Reviewed Original ResearchMeSH Keywords5-MethylcytosineAnimalsBase SequenceConserved SequenceCpG IslandsCytosineDatabases, GeneticDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEpigenesis, GeneticGene Expression RegulationHematopoietic Stem CellsHistonesHumansLeukemiaMaleMiceMice, Inbred C57BLMice, Mutant Strains
2012
Less Is More: Unveiling the Functional Core of Hematopoietic Stem Cells through Knockout Mice
Rossi L, Lin K, Boles N, Yang L, King K, Jeong M, Mayle A, Goodell M. Less Is More: Unveiling the Functional Core of Hematopoietic Stem Cells through Knockout Mice. Cell Stem Cell 2012, 11: 302-317. PMID: 22958929, PMCID: PMC3461270, DOI: 10.1016/j.stem.2012.08.006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHematopoietic stem cellsHSC functionSomatic stem cell typesCell cycle controlStem cellsPTEN/AKTKey regulatory pathwaysStem cell typesTGF-β signalingKnockout miceHSC biologyRegulatory pathwaysCycle controlGenetic analysisCell typesFunctional coreFunctional modulesCellsWntCohesive pictureGenesSignalingBiologyAktMice