2024
The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer
Feng B, Bai Z, Zhou X, Zhao Y, Xie Y, Huang X, Liu Y, Enbar T, Li R, Wang Y, Gao M, Bonati L, Peng M, Li W, Tao B, Charmoy M, Held W, Melenhorst J, Fan R, Guo Y, Tang L. The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer. Nature 2024, 634: 712-720. PMID: 39322665, PMCID: PMC11485240, DOI: 10.1038/s41586-024-07962-4.Peer-Reviewed Original ResearchCD8+ T cellsMammalian target of rapamycinCancer immunotherapyT cellsNext-generation cancer immunotherapyAdoptive T-cell transferImmune checkpoint blockade therapyLong-term complete remissionCurrent cancer immunotherapiesCheckpoint blockade therapyInduce durable remissionsT-cell transferCD8+ TCytokine-based immunotherapyType 2 cytokinesXenograft tumor modelBlockade therapyDurable remissionsComplete remissionAntitumour efficacyTumor modelTarget of rapamycinInterleukin-4Immune responseCD8Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission
Bai Z, Feng B, McClory S, de Oliveira B, Diorio C, Gregoire C, Tao B, Yang L, Zhao Z, Peng L, Sferruzza G, Zhou L, Zhou X, Kerr J, Baysoy A, Su G, Yang M, Camara P, Chen S, Tang L, June C, Melenhorst J, Grupp S, Fan R. Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission. Nature 2024, 634: 702-711. PMID: 39322664, PMCID: PMC11485231, DOI: 10.1038/s41586-024-07762-w.Peer-Reviewed Original ResearchChimeric antigen receptorChimeric antigen receptor T cellsT cellsIL-4CAR T-cell dysfunctionChimeric antigen receptor T-cell productsCAR-T cell persistenceProteomic profiling of seraCAR-T cellsT cell persistenceT-cell therapyLong-term remissionT cell dysfunctionCAR-T productsType 2 cytokinesAntigen-specific activationT cell productionAssociated with patientsType 2 cellsDysfunctional subsetPotential therapeutic strategyCellular immunotherapyLeukemia remissionPatients relapseType 2 functionsSpatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues
Bai Z, Zhang D, Gao Y, Tao B, Zhang D, Bao S, Enninful A, Wang Y, Li H, Su G, Tian X, Zhang N, Xiao Y, Liu Y, Gerstein M, Li M, Xing Y, Lu J, Xu M, Fan R. Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues. Cell 2024 PMID: 39353436, DOI: 10.1016/j.cell.2024.09.001.Peer-Reviewed Original ResearchRNA biologyWhole-transcriptome sequencingMicroRNA regulatory networkSplicing dynamicsDeterministic barcodingRNA speciesRNA processingRNA variantsFFPE tissuesRegulatory networksTranscriptome sequencingSpliced isoformsNon-malignant cellsTumor clonal architecturesClonal architectureGene expressionCellular dynamicsRNAArchival formalin-fixed paraffin-embedded tissueMalignant subclonesFormalin-fixed paraffin-embedded (FFPEFFPE samplesParaffin-embedded (FFPEBiologyHuman lymphomasSpatially resolved epigenome sequencing via Tn5 transposition and deterministic DNA barcoding in tissue
Farzad N, Enninful A, Bao S, Zhang D, Deng Y, Fan R. Spatially resolved epigenome sequencing via Tn5 transposition and deterministic DNA barcoding in tissue. Nature Protocols 2024, 19: 3389-3425. PMID: 38943021, DOI: 10.1038/s41596-024-01013-y.Peer-Reviewed Original ResearchTn5 transpositionDeterministic barcodingGenome-wide profiling of histone modificationsProfiling of histone modificationsTransposase-accessible chromatin sequencingEpigenomic profiling methodsGenome-wide profilingSingle-base resolutionGene regulation programsGenomic DNA locusNext-generation sequencingDNA lociBioinformatics skillsLibrary preparationDNA barcodingChromatin accessibilityChromatin sequencingHistone modificationsEpigenome sequencingEpigenetic landscapeEpigenetic mapsCellular functionsEpigenetic markersCustom pipelineBarcodingSenNet recommendations for detecting senescent cells in different tissues
Suryadevara V, Hudgins A, Rajesh A, Pappalardo A, Karpova A, Dey A, Hertzel A, Agudelo A, Rocha A, Soygur B, Schilling B, Carver C, Aguayo-Mazzucato C, Baker D, Bernlohr D, Jurk D, Mangarova D, Quardokus E, Enninga E, Schmidt E, Chen F, Duncan F, Cambuli F, Kaur G, Kuchel G, Lee G, Daldrup-Link H, Martini H, Phatnani H, Al-Naggar I, Rahman I, Nie J, Passos J, Silverstein J, Campisi J, Wang J, Iwasaki K, Barbosa K, Metis K, Nernekli K, Niedernhofer L, Ding L, Wang L, Adams L, Ruiyang L, Doolittle M, Teneche M, Schafer M, Xu M, Hajipour M, Boroumand M, Basisty N, Sloan N, Slavov N, Kuksenko O, Robson P, Gomez P, Vasilikos P, Adams P, Carapeto P, Zhu Q, Ramasamy R, Perez-Lorenzo R, Fan R, Dong R, Montgomery R, Shaikh S, Vickovic S, Yin S, Kang S, Suvakov S, Khosla S, Garovic V, Menon V, Xu Y, Song Y, Suh Y, Dou Z, Neretti N. SenNet recommendations for detecting senescent cells in different tissues. Nature Reviews Molecular Cell Biology 2024, 1-23. PMID: 38831121, DOI: 10.1038/s41580-024-00738-8.Peer-Reviewed Original ResearchSenescent cellsDetect senescent cellsIrreversible cell cycle arrestCellular senescenceCell cycle arrestSenescence markersBiomarker Working GroupCycle arrestCellular senescence markersBiological processesCell biologyPostmitotic cellsSenescent phenotypeCirculating markersTissue culture studiesSenescence signatureSenescenceCellsMorphological featuresDetrimental roleTissueMarkersSeasonal investigationMLL1 regulates cytokine-driven cell migration and metastasis
Nair P, Danilova L, Gómez-de-Mariscal E, Kim D, Fan R, Muñoz-Barrutia A, Fertig E, Wirtz D. MLL1 regulates cytokine-driven cell migration and metastasis. Science Advances 2024, 10: eadk0785. PMID: 38478601, PMCID: PMC10936879, DOI: 10.1126/sciadv.adk0785.Peer-Reviewed Original ResearchConceptsMethyltransferase mixed-lineage leukemia 1Cell migrationControls actin filament assemblyRegulation of cell migrationHistone methyltransferase mixed-lineage leukemia 1Actin filament assemblyCell cycle-related pathwaysCancer cell migrationMixed-lineage leukemia 1Regulating cell proliferationMyosin contractilityFilament assemblyProtein meninAssociated with immune cellsMetastatic burdenCancer cellsCell proliferationPrimary tumor growth rateLung metastatic burdenTumor growth rateGrowth rateCellsPreexisting metastasesMetastatic diseaseTumor growthAuthor Correction: Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments
Janiszewska M, Tabassum D, Castaño Z, Cristea S, Yamamoto K, Kingston N, Murphy K, Shu S, Harper N, Del Alcazar C, Alečković M, Ekram M, Cohen O, Kwak M, Qin Y, Laszewski T, Luoma A, Marusyk A, Wucherpfennig K, Wagle N, Fan R, Michor F, McAllister S, Polyak K. Author Correction: Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nature Cell Biology 2024, 26: 841-841. PMID: 38443568, DOI: 10.1038/s41556-024-01385-z.Peer-Reviewed Original Research
2023
229 Large-scale omics profiling reveals type-2 functionality sustaining 8-year leukemia remission following CAR T cell therapy
Bai Z, Feng B, McClory S, Diorio C, Zhao Z, Tang L, Melenhorst J, June C, Grupp S, Fan R. 229 Large-scale omics profiling reveals type-2 functionality sustaining 8-year leukemia remission following CAR T cell therapy. 2023, a261-a264. DOI: 10.1136/jitc-2023-sitc2023.0229.Peer-Reviewed Original ResearchSingle-Cell Multi-Omics Reveals Type-2 Functionality in Maintaining CAR T Cell Longevity Associated with 8-Year Leukemia Remission
Bai Z, Feng B, Mcclory S, Diorio C, Zhao Z, Tang L, Melenhorst J, June C, Grupp S, Fan R. Single-Cell Multi-Omics Reveals Type-2 Functionality in Maintaining CAR T Cell Longevity Associated with 8-Year Leukemia Remission. Blood 2023, 142: 352. DOI: 10.1182/blood-2023-179480.Peer-Reviewed Original ResearchChimeric antigen receptor T cellsCAR-T cellsChimeric antigen receptorType 2 cytokinesB-cell aplasiaT cellsAcute lymphocytic leukemiaCAR-T persistenceIL-4CAR-TType 1Validation cohortCAR T infusionSurvival of tumor-bearing miceDiscovery cohortPersistent CAR T cellsDose of tumor cellsLevels of type 2 cytokinesType 2 cytokine levelsNSG mouse modelPediatric ALL patientsLong-term remissionReduced tumor burdenT cell longevityType 1 cytokinesMapping RNA translation
Fan R. Mapping RNA translation. Science 2023, 380: 1321-1322. PMID: 37384700, DOI: 10.1126/science.adi6844.Peer-Reviewed Original ResearchMicrotechnologies for single-cell and spatial multi-omics
Deng Y, Bai Z, Fan R. Microtechnologies for single-cell and spatial multi-omics. Nature Reviews Bioengineering 2023, 1: 769-784. DOI: 10.1038/s44222-023-00084-y.Peer-Reviewed Original ResearchSuch single-cell dataGene regulatory networksMulti-omics assaysSingle-cell dataMulti-omics studiesSingle cellsContext of tissuesGenome scaleRegulatory networksOmics informationGene expressionOmics assaysCellular profilingSubcellular levelIntact tissueCellsFunctional stateAssaysOmicsMicroarrayTissueProfilingRegulationExpressionMicrofluidic platformMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.Peer-Reviewed Original ResearchConceptsB cell depletion therapyAcute COVID infectionAnti-spike IgGHigh-risk patientsCoronavirus disease-19COVID-19 pathologyDepletion therapyVaccine protectionAntibody responseCOVID infectionHematologic malignanciesImmune protectionDisease-19Healthy donorsMultiple time pointsSerology assaysBlood samplesSoluble markersB cellsImmunization strategiesPatientsFunctional deficiencySerological analysisTime pointsClonotype diversityThe technological landscape and applications of single-cell multi-omics
Baysoy A, Bai Z, Satija R, Fan R. The technological landscape and applications of single-cell multi-omics. Nature Reviews Molecular Cell Biology 2023, 24: 695-713. PMID: 37280296, PMCID: PMC10242609, DOI: 10.1038/s41580-023-00615-w.Peer-Reviewed Original ResearchConceptsSingle-cell multi-omics technologiesMulti-omics technologiesMolecular cell biology researchCell lineage tracingCell biology researchBioinformatics toolsLineage tracingOmics methodsCell statesBiology researchMathematical modellingCancer geneticsOmics modalitiesComputational methodsEpitranscriptomeEpigenomeTranscriptomeGenomeProteomeOmicsOptimization of throughputGeneticsArt methodsTranslational researchUniquenessSecretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production
Kang Y, Paik H, Zhang S, Chen J, Olson O, Mitchell C, Collins A, Swann J, Warr M, Fan R, Passegué E. Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production. Journal Of Experimental Medicine 2023, 220: e20230088. PMID: 37115584, PMCID: PMC10140385, DOI: 10.1084/jem.20230088.Peer-Reviewed Original ResearchConceptsGranulocyte/macrophage progenitorsHematopoietic stem cellsMyeloid differentiationMajor functional contributorsNovel regulatory functionLocal bone marrow (BM) microenvironmentSteady-state hematopoiesisDifferentiation trajectoriesRecent lineagesMyeloid cell productionCellular heterogeneityBone marrow microenvironmentRegulatory functionsFunctional contributorsMacrophage progenitorsSecretory cellsStem cellsMPP3Blood productionMarrow microenvironmentCell productionDifferentiationRapid productionDistinct subsetsMyelopoiesisSpecial Issue: Spatial Omics
Fan R, Bayraktar O. Special Issue: Spatial Omics. GEN Biotechnology 2023, 2: 61-62. DOI: 10.1089/genbio.2023.29076.cfp2.Peer-Reviewed Original ResearchSpatial epigenome–transcriptome co-profiling of mammalian tissues
Zhang D, Deng Y, Kukanja P, Agirre E, Bartosovic M, Dong M, Ma C, Ma S, Su G, Bao S, Liu Y, Xiao Y, Rosoklija G, Dwork A, Mann J, Leong K, Boldrini M, Wang L, Haeussler M, Raphael B, Kluger Y, Castelo-Branco G, Fan R. Spatial epigenome–transcriptome co-profiling of mammalian tissues. Nature 2023, 616: 113-122. PMID: 36922587, PMCID: PMC10076218, DOI: 10.1038/s41586-023-05795-1.Peer-Reviewed Original ResearchConceptsGene expressionSingle-cell resolutionChromatin accessibilityJoint profilingHistone modificationsGene regulationCellular statesEpigenetic mechanismsCentral dogmaSpatial transcriptomeTranscriptional phenotypeCell statesOmics informationSpatial transcriptomicsEpigenetic primingMammalian tissuesEpigenomeMolecular biologyTissue architectureCell dynamicsMechanistic relationshipDifferential rolesNew insightsMouse brainProfilingHigh-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq
Liu Y, DiStasio M, Su G, Asashima H, Enninful A, Qin X, Deng Y, Nam J, Gao F, Bordignon P, Cassano M, Tomayko M, Xu M, Halene S, Craft J, Hafler D, Fan R. High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq. Nature Biotechnology 2023, 41: 1405-1409. PMID: 36823353, PMCID: PMC10567548, DOI: 10.1038/s41587-023-01676-0.Peer-Reviewed Original ResearchCXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis
Dunbar A, Kim D, Lu M, Farina M, Bowman R, Yang J, Park Y, Karzai A, Xiao W, Zaroogian Z, O’Connor K, Mowla S, Gobbo F, Verachi P, Martelli F, Sarli G, Xia L, Elmansy N, Kleppe M, Chen Z, Xiao Y, McGovern E, Snyder J, Krishnan A, Hill C, Cordner K, Zouak A, Salama M, Yohai J, Tucker E, Chen J, Zhou J, McConnell T, Migliaccio A, Koche R, Rampal R, Fan R, Levine R, Hoffman R. CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis. Blood 2023, 141: 2508-2519. PMID: 36800567, PMCID: PMC10273167, DOI: 10.1182/blood.2022015418.Peer-Reviewed Original ResearchConceptsConstitutive JAK/STATHematopoietic stem/progenitor cellsJAK/STATBone marrow fibrosisStem/progenitor cellsMPN cellsMarrow fibrosisHuman cancersMyeloproliferative neoplasmsPrimary cellsProgenitor cellsMechanistic insightsPharmacologic inhibitionGenetic deletionSignaling contributesGene signatureJAK inhibitor therapyTherapeutic targetingEnhanced proliferationCritical roleTherapeutic targetCXCL8/MF developmentMF pathogenesisInhibitor therapyAnti-seed PNAs targeting multiple oncomiRs for brain tumor therapy
Wang Y, Malik S, Suh H, Xiao Y, Deng Y, Fan R, Huttner A, Bindra R, Singh V, Saltzman W, Bahal R. Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy. Science Advances 2023, 9: eabq7459. PMID: 36753549, PMCID: PMC9908025, DOI: 10.1126/sciadv.abq7459.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryHigh recurrence rateOrthotopic mouse modelBrain tumor therapyTreatment of glioblastomaRecurrence ratePoor survivalLethal malignancyMouse modelGBM progressionTumor cellsGlioblastomaTumor therapyBioadhesive nanoparticlesOncomiRSurvivalTreatmentSeed regionMalignancyTemozolomideTherapySpecial Issue: Spatial Omics
Fan R, Bayraktar O. Special Issue: Spatial Omics. GEN Biotechnology 2023, 2: 3-4. DOI: 10.1089/genbio.2023.29076.cfp.Peer-Reviewed Original Research