2016
Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies
Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC. Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Blood 2016, 128: 783-793. PMID: 27301863, PMCID: PMC4982452, DOI: 10.1182/blood-2015-10-676304.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsT cell developmentPluripotent stem cellsT cell receptorStem cellsOmenn syndrome patientsSingle-strand DNA breaksHuman induced pluripotent stem cellsControl iPSCsDeep-sequencing analysisT lineage cellsHuman T-cell developmentT cell progenitorsIPSC-derived cellsJoining genesImpaired T-cell differentiationDNA breaksSame geneN-terminalImmune system developmentLocus rearrangementT cell differentiationPatient cellsRecombination activityGenetic defects
2009
Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation
Giblin W, Chatterji M, Westfield G, Masud T, Theisen B, Cheng HL, DeVido J, Alt FW, Ferguson DO, Schatz DG, Sekiguchi J. Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood 2009, 113: 2965-2975. PMID: 19126872, PMCID: PMC2662642, DOI: 10.1182/blood-2008-07-165167.Peer-Reviewed Original ResearchConceptsDouble-strand breaksHypomorphic RAG1 mutationsImmune system dysfunctionDNA rearrangementsKnockin mouse modelP53 mutant backgroundAberrant DNA rearrangementsDNA double-strand breaksPremature immunosenescenceDNA end processingSystem dysfunctionRecombination signal sequencesMouse modelRAG1 mutationsImmune systemMice exhibitAntigen receptor genesThymic lymphomasTumor developmentVivo evidenceMutant backgroundLymphocyte developmentSignal sequenceReceptor geneHypomorphic mutations
2005
Biochemistry of V(D)J Recombination
Schatz DG, Spanopoulou E. Biochemistry of V(D)J Recombination. Current Topics In Microbiology And Immunology 2005, 290: 49-85. PMID: 16480039, DOI: 10.1007/3-540-26363-2_4.Peer-Reviewed Original Research
2004
Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes
Shockett PE, Zhou S, Hong X, Schatz DG. Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes. Molecular Immunology 2004, 40: 813-829. PMID: 14687938, DOI: 10.1016/j.molimm.2003.09.009.Peer-Reviewed Original ResearchConceptsPeripheral lymphoid organsIGK locusInducible gene expressionLymph nodesCell reconstitutionLymphoid organsTransgenic miceTRB locusTRD locusT-cell reconstitutionB-cell reconstitutionMammalian cellsRAG-deficient miceSignal endsTra locusRecombination signalsInducible activationGene expressionTCR beta chainFunctional expressionLymphocyte developmentLociRAG2 mRNALymphocyte reconstitutionTransgene
2003
A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences
Lee AI, Fugmann SD, Cowell LG, Ptaszek LM, Kelsoe G, Schatz DG. A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences. PLOS Biology 2003, 1: e1. PMID: 14551903, PMCID: PMC212687, DOI: 10.1371/journal.pbio.0000001.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSignal sequenceGene segmentsProtein-DNA interactionsLevel of recombinationDegree of conservationParticular functional importanceJ gene segmentsAntigen receptor genesSpacer variantsRAG proteinsRecombination machineryRSS activityInactive pseudogeneRSS functionSpacer sequencesFunctional analysisInteraction surfaceFunctional importanceLymphocyte developmentNumerous complex interactionsBiochemical assaysDistinct cooperationReceptor geneHeptamer
2000
Genetic Modulation of T Cell Receptor Gene Segment Usage during Somatic Recombination
Livak F, Burtrum D, Rowen L, Schatz D, Petrie H. Genetic Modulation of T Cell Receptor Gene Segment Usage during Somatic Recombination. Journal Of Experimental Medicine 2000, 192: 1191-1196. PMID: 11034609, PMCID: PMC2195867, DOI: 10.1084/jem.192.8.1191.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesFlanking recombination signal sequencesGene segment usageUseful gene productsLymphocyte antigen receptorsSegment usageSignal sequenceSomatic cellsCombinatorial joiningGene productsSomatic recombinationRecombinase activityGenetic modulationGene segmentsBeta gene segment usageMature T lymphocytesD betaSynaptic complexGermline genesTotal repertoireNaive repertoireAntigen receptorRecombinationRepertoireBiased representation
1999
Developing B-cell theories
Schatz D. Developing B-cell theories. Nature 1999, 400: 615-617. PMID: 10458155, DOI: 10.1038/23134.Commentaries, Editorials and LettersCharacterization of TCR gene rearrangements during adult murine T cell development.
Livák F, Tourigny M, Schatz D, Petrie H. Characterization of TCR gene rearrangements during adult murine T cell development. The Journal Of Immunology 1999, 162: 2575-80. PMID: 10072498, DOI: 10.4049/jimmunol.162.5.2575.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Rearrangement, beta-Chain T-Cell Antigen ReceptorGene Rearrangement, delta-Chain T-Cell Antigen ReceptorGene Rearrangement, gamma-Chain T-Cell Antigen ReceptorGene Rearrangement, T-LymphocyteHyaluronan ReceptorsMiceMice, Inbred C57BLPolymerase Chain ReactionReceptors, Interleukin-2T-LymphocytesConceptsTCRbeta locusTCRdelta locusGammadelta T cell lineagesMurine T cell developmentTCR gene rearrangementsT lineage cellsGene rearrangementsT cell developmentLineage decisionsLocus recombinationLineage commitmentProductive rearrangementsIrreversible commitmentCell lineagesDelta geneMolecular evidenceCell developmentTCRbeta rearrangementsDevelopmental stagesT-cell lineageTCR complexLociLineage cellsLineagesGenes
1996
Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo.
Hoffman ES, Passoni L, Crompton T, Leu TM, Schatz DG, Koff A, Owen MJ, Hayday AC. Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes & Development 1996, 10: 948-962. PMID: 8608942, DOI: 10.1101/gad.10.8.948.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, T-LymphocyteCell CycleCell SeparationClone CellsCyclinsDNA-Binding ProteinsFemaleFlow CytometryFluorescent Antibody Technique, IndirectGene Expression Regulation, DevelopmentalGene Rearrangement, beta-Chain T-Cell Antigen ReceptorHomeodomain ProteinsHyaluronan ReceptorsMiceMice, Inbred C57BLProteinsReceptors, Antigen, T-Cell, alpha-betaReceptors, Interleukin-2Retinoblastoma ProteinRNA, MessengerT-LymphocytesThymus GlandConceptsTCRbeta chain genesBeta selectionT-cell receptor beta-chain locusChain geneTCRbeta chain gene rearrangementAlpha beta T cell developmentProductive gene rearrangementHyperphosphorylation of RbGene rearrangementsTCR gene rearrangementsTransition of thymocytesTCRbeta gene rearrangementT cell developmentRegulation of p27Coincident regulationBeta-chain locusPopulation of cellsTCR lociCell cycleCdc2 activityCDK2 activityTCRbeta selectionCyclin AThymocyte expansionCell phenotypeT-Cell Receptor α Locus V(D)J Recombination By-Products Are Abundant in Thymocytes and Mature T Cells
Livak F, Schatz D. T-Cell Receptor α Locus V(D)J Recombination By-Products Are Abundant in Thymocytes and Mature T Cells. Molecular And Cellular Biology 1996, 16: 609-618. PMID: 8552089, PMCID: PMC231040, DOI: 10.1128/mcb.16.2.609.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceDNA DamageGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorImmune SystemMiceMice, Inbred C57BLMolecular Probe TechniquesMolecular Sequence DataReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaRecombination, GeneticT-LymphocytesThymus GlandConceptsRecombination signal sequencesSignal sequenceDNA moleculesAlpha locusTCR alpha/delta locusAlpha/delta locusBroken DNA moleculesReciprocal productsJ alpha locusTermination of expressionT-cell receptor α locusC delta regionTCR alpha locusSouthern blot analysisT cell developmentGenome integrityDNA existΑ locusQuantitative Southern blot analysisT-cell receptor genesCoding regionsDevelopmental transitionsLymphoid developmentDelta locusRAG-2
1995
In-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision
Livak F, Petrie H, Crisps I, Schatz D. In-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision. Immunity 1995, 2: 617-627. PMID: 7796295, DOI: 10.1016/1074-7613(95)90006-3.Peer-Reviewed Original ResearchConceptsT cell lineage decisionsCell lineage decisionsLineage decisionsRandom gene rearrangementsSouthern blot analysisT cell receptor complexCell receptor complexGene rearrangementsDelta locusLocus sequenceGamma delta lineageReceptor complexT cell receptorBlot analysisDistinct precursorsCommon precursorCell receptorCritical roleDelta rearrangementsDelta lineageRearrangementΔ gene rearrangementAlpha betaT cellsGamma delta T-cell receptor
1989
The V(D)J recombination activating gene, RAG-1
Schatz D, Oettinger M, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell 1989, 59: 1035-1048. PMID: 2598259, DOI: 10.1016/0092-8674(89)90760-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCell LineCloning, MolecularDNA NucleotidyltransferasesGene Expression RegulationGene LibraryGene Rearrangement, T-LymphocyteGenes, ImmunoglobulinGenomic LibraryHumansMiceMolecular Sequence DataNucleic Acid HybridizationOligonucleotide ProbesReceptors, Antigen, T-CellRecombination, GeneticSequence Homology, Nucleic AcidT-LymphocytesTransfectionVDJ Recombinases