2020
N6-methyladenine in DNA antagonizes SATB1 in early development
Li Z, Zhao S, Nelakanti RV, Lin K, Wu TP, Alderman MH, Guo C, Wang P, Zhang M, Min W, Jiang Z, Wang Y, Li H, Xiao AZ. N6-methyladenine in DNA antagonizes SATB1 in early development. Nature 2020, 583: 625-630. PMID: 32669713, PMCID: PMC8596487, DOI: 10.1038/s41586-020-2500-9.Peer-Reviewed Original ResearchConceptsN6-mAN6-methyladenineMouse trophoblast stem cellsLarge chromatin domainsCell fate transitionsLarge-scale chromatinUnexpected molecular mechanismTrophoblast stem cellsEarly embryonic developmentDNA secondary structuresEarly developmentFate transitionsMammalian genomesChromatin domainsEpigenetic landscapeGene regulationChromatin organizerEmbryonic developmentDNA modificationsBiological roleMolecular mechanismsSATB1 functionsMolecular pathwaysCell culture modelSecondary structurem6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liverMammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA
Zhang M, Yang S, Nelakanti R, Zhao W, Liu G, Li Z, Liu X, Wu T, Xiao A, Li H. Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell Research 2020, 30: 197-210. PMID: 32051560, PMCID: PMC7054317, DOI: 10.1038/s41422-019-0237-5.Peer-Reviewed Original ResearchConceptsN6-mAMammalian genomesStructure-based mutagenesis studiesBase unpairing regionsChromosome regulationDNA demethylasesStructural studiesEpigenetic marksDNA demethylaseMouse genomeEarly embryogenesisGenomic studiesBase flippingN6-methyladenineALKBH1Mutagenesis studiesFlipped baseGenomeProfiling studiesDNACatalytic centerDemethylaseActive regulationRegulationDemethylases
2018
Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo
Kooreman NG, Kim Y, de Almeida PE, Termglinchan V, Diecke S, Shao NY, Wei TT, Yi H, Dey D, Nelakanti R, Brouwer TP, Paik DT, Sagiv-Barfi I, Han A, Quax PHA, Hamming JF, Levy R, Davis MM, Wu JC. Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo. Cell Stem Cell 2018, 22: 501-513.e7. PMID: 29456158, PMCID: PMC6134179, DOI: 10.1016/j.stem.2018.01.016.Peer-Reviewed Original ResearchConceptsElicit anti-tumor responsesAnti-tumor responseInduced pluripotent stem cellsTumor growthMetastatic tumor loadTumor-associated antigensAnti-tumor vaccinesMurine breast cancerTumor-bearing miceAutologous induced pluripotent stem cellsUnvaccinated recipientsProphylactic settingAdoptive transferClinical immunotherapyCancer vaccinesTumor loadMelanoma recurrenceBreast cancerResection siteMelanoma modelMyeloid cellsCell responsesVaccineCancer cellsCancer
2017
Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics
Kooreman NG, de Almeida PE, Stack JP, Nelakanti RV, Diecke S, Shao NY, Swijnenburg RJ, Sanchez-Freire V, Matsa E, Liu C, Connolly AJ, Hamming JF, Quax PHA, Brehm MA, Greiner DL, Shultz LD, Wu JC. Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics. Cell Reports 2017, 20: 1978-1990. PMID: 28834758, PMCID: PMC5573767, DOI: 10.1016/j.celrep.2017.08.003.Peer-Reviewed Original ResearchConceptsHuman immune responseHumanized miceImmune cellsImmune responseStem cell allograftsInnate immune cellsAllogeneic stem cellsStem cellsMouse immune systemAlloimmune responseCell allograftsImmunodeficient miceMouse modelGraft persistenceImmune systemHuman lymphocytesMiceAllograftsStem cell therapeuticsCell therapeuticsPluripotent stem cellsEmbryonic stem cellsCellsAlloimmunityResponse