2024
Gene trajectory inference for single-cell data by optimal transport metrics
Qu R, Cheng X, Sefik E, Stanley III J, Landa B, Strino F, Platt S, Garritano J, Odell I, Coifman R, Flavell R, Myung P, Kluger Y. Gene trajectory inference for single-cell data by optimal transport metrics. Nature Biotechnology 2024, 1-11. PMID: 38580861, PMCID: PMC11452571, DOI: 10.1038/s41587-024-02186-3.Peer-Reviewed Original ResearchGene dynamicsGene programTrajectory inferenceBiological processesCell-cell graphDynamics of genesCell trajectory inferenceSingle-cell RNA sequencingSingle-cell dataCell state transitionsMyeloid lineage maturationDynamics of biological processesGene distributionRNA sequencingPseudotemporal orderingGene processingTrajectories of cellsGenesActivity of biological processesTechnical noiseGroups of cellsLineage maturationCellsConstruct cellsSequence
2023
Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCellsMETTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells
Xiao Z, Wang S, Tian Y, Lv W, Sheng H, Zhan M, Huang Q, Zhang Z, Zhu L, Zhu C, Zhong H, Wen Q, Liu Z, Tan J, Xu Y, Yang M, Liu Y, Flavell R, Yang Q, Cao G, Yin Z. METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells. Cell Reports 2023, 42: 112684. PMID: 37355989, DOI: 10.1016/j.celrep.2023.112684.Peer-Reviewed Original ResearchConceptsM6A methylationMRNA stabilityΓδ T17 cellsEndogenous double-stranded RNADouble-stranded RNAActivation of STAT1MRNA metabolismMRNA turnoverGene expressionKey enzymeDsRNA contentT17 cellsMethylationFunctional specializationRNA contentΓδ TCritical roleMETTL3Numerous aspectsCellsT17Distinct subsetsM6ATranscriptsRNAGasdermin D licenses MHCII induction to maintain food tolerance in small intestine
He K, Wan T, Wang D, Hu J, Zhou T, Tao W, Wei Z, Lu Q, Zhou R, Tian Z, Flavell R, Zhu S. Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. Cell 2023, 186: 3033-3048.e20. PMID: 37327784, DOI: 10.1016/j.cell.2023.05.027.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsCleavage fragmentsSmall intestineCaspase-3/7 inhibitorRegulatory hubTolerance phenotypeN-terminal fragmentHost cellsDifferential cleavageCaspase-3/7Upper small intestineTranscription of CIITAGasdermin DEpithelial cellsMHCII deficiencyMHCII inductionDietary antigensTr1 cellsImmune toleranceProtective immunityFood toleranceForeign antigensMHCII moleculesMiceCells
2022
Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis
Nechanitzky R, Nechanitzky D, Ramachandran P, Duncan G, Zheng C, Göbl C, Gill K, Haight J, Wakeham A, Snow B, Bradaschia-Correa V, Ganguly M, Lu Z, Saunders M, Flavell R, Mak T. Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis. Cell Death & Differentiation 2022, 30: 407-416. PMID: 36528755, PMCID: PMC9950465, DOI: 10.1038/s41418-022-01092-y.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisTh17 cellsMultiple sclerosisAutoimmune encephalomyelitisChAT expressionBrain-infiltrating immune cellsStrong TCR signalingCholinergic controlTherapeutic immunomodulationCholine acetyltransferaseImmune cellsCell pathogenicityDisease progressionChronic activationMouse modelTranscription factor Bhlhe40Novel targetAcetylcholineMRNA levelsPathogenic determinantsTCR signalingEncephalomyelitisCellsExpressionIL17tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis
Liu Y, Zhou J, Li X, Zhang X, Shi J, Wang X, Li H, Miao S, Chen H, He X, Dong L, Lee GR, Zheng J, Liu RJ, Su B, Ye Y, Flavell RA, Yi C, Wu Y, Li HB. tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. Nature Immunology 2022, 23: 1433-1444. PMID: 36138184, DOI: 10.1038/s41590-022-01301-3.Peer-Reviewed Original ResearchConceptsCell expansionKey functional proteinsVivo physiological roleDe novo protein productionCell cycle arrestTranslational controlRNA modificationsMyc proteinFunctional proteinsTranslation efficiencyKey proteinsCell homeostasisProtein productionPhysiological roleProtein synthesisProliferative stateCycle arrestConditional deletionT cell homeostasisNaive T cellsProteinQuiescent stateSpecific subsetT cellsCells
2014
NLRP6 Inflammasome Orchestrates the Colonic Host-Microbial Interface by Regulating Goblet Cell Mucus Secretion
Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP, Brown EM, Frankel G, Levy M, Katz MN, Philbrick WM, Elinav E, Finlay BB, Flavell RA. NLRP6 Inflammasome Orchestrates the Colonic Host-Microbial Interface by Regulating Goblet Cell Mucus Secretion. Cell 2014, 156: 1045-1059. PMID: 24581500, PMCID: PMC4017640, DOI: 10.1016/j.cell.2014.01.026.Peer-Reviewed Original ResearchConceptsRegulatory pathwaysGoblet cell mucus secretionHost-microbial mutualismHost-microbial interfaceNLRP6 inflammasomeMucus secretionGoblet cellsBiogeographical distributionProkaryotic cellsInnate immune playersNLRP6 deficiencyGranule exocytosisImmune regulatory pathwaysInflammasome-deficient miceColonic microbiota compositionLarge intestinal lumenCritical orchestratorsImmune playersPersistent infectionMucus productionCellsIntestinal lumenPathwayMucosal surfacesMicrobiota composition