2024
Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulated
2021
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancerPolycomb complexes redundantly maintain epidermal stem cell identity during development
Cohen I, Bar C, Liu H, Valdes VJ, Zhao D, Galbo PM, Silva JM, Koseki H, Zheng D, Ezhkova E. Polycomb complexes redundantly maintain epidermal stem cell identity during development. Genes & Development 2021, 35: 354-366. PMID: 33602871, PMCID: PMC7919412, DOI: 10.1101/gad.345363.120.Peer-Reviewed Original ResearchConceptsFunctional redundancyTranscription factorsRepressive chromatin domainsStem cell identityEpidermal stem cellsStrong derepressionEpidermal identityPolycomb complexesChromatin domainsDevelopmental regulatorsIdentity genesPRC2 functionGene repressionGenomic bindingCell identityMolecular dissectionEpidermal progenitorsLineage identityPRC2PRC1Ectopic expressionSevere defectsEpidermal stratificationPhysiological significanceStem cells
2019
Lung Mammary Metastases but Not Primary Tumors Induce Accumulation of Atypical Large Platelets and Their Chemokine Expression
Zheng W, Zhang H, Zhao D, Zhang J, Pollard JW. Lung Mammary Metastases but Not Primary Tumors Induce Accumulation of Atypical Large Platelets and Their Chemokine Expression. Cell Reports 2019, 29: 1747-1755.e4. PMID: 31722193, PMCID: PMC6919330, DOI: 10.1016/j.celrep.2019.10.016.Peer-Reviewed Original ResearchConceptsTumor microenvironmentLung metastasesEndothelial cellsLarge plateletsPrimary mammary tumorsEndothelial progenitor cellsConsiderable cellular heterogeneityMammary cancer metastasisAuthentic endothelial cellsMammary metastasesMetastatic sitesChemokine expressionMammary tumorsMetastatic growthMetastasisTherapeutic interventionsCellular playersCD44 upregulationCancer metastasisProgenitor cellsPlateletsInduces accumulationIndirect mechanismsDistinct gene expression programsCD44Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression
Bar C, Cohen I, Zhao D, Pothula V, Litskevitch A, Koseki H, Zheng D, Ezhkova E. Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression. Cell Reports 2019, 28: 257-266.e5. PMID: 31269445, PMCID: PMC6921245, DOI: 10.1016/j.celrep.2019.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCell CycleChromatin ImmunoprecipitationChromatin Immunoprecipitation SequencingCyclin-Dependent Kinase Inhibitor p16Epigenesis, GeneticEpitheliumGene Expression Regulation, DevelopmentalGene OntologyHedgehog ProteinsMiceMice, KnockoutMicroscopy, Electron, ScanningPolycomb Repressive Complex 1Polycomb Repressive Complex 2RNA-SeqSignal TransductionTaste BudsTongueConceptsGene expressionPolycomb Repressive Complex 1Spatial gene expression patternsRepressive Complex 1Gene expression patternsCell gene expressionChromatin regulatorsTissue patterningSonic hedgehog expressionEpigenetic regulationNiche structureExpression patternsCell genesEpithelial progenitorsHedgehog expressionShhEctopic ShhTaste cellsPapilla structuresTissue patternsExpressionCellsPatterningProper maintenanceComplexes 1Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling
Nguyen MB, Valdes VJ, Cohen I, Pothula V, Zhao D, Zheng D, Ezhkova E. Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling. Experimental Dermatology 2019, 28: 374-382. PMID: 30758073, PMCID: PMC6488392, DOI: 10.1111/exd.13901.Peer-Reviewed Original ResearchConceptsCell formationCommon genetic programPaw skinMerkel cellsLineage-tracing experimentsBack skinTranscriptome studiesMerkel cell developmentGenetic programMAPK signalingPrimary hair folliclesCell developmentSpecialized structuresMechanosensory cellsSimilar regulatorsUpstream factorsCritical functionsPrecursor cellsFGFR2SignalingCellsTouch domesGlabrous skinMurineHair follicles
2018
PRC1 preserves epidermal tissue integrity independently of PRC2
Cohen I, Zhao D, Menon G, Nakayama M, Koseki H, Zheng D, Ezhkova E. PRC1 preserves epidermal tissue integrity independently of PRC2. Genes & Development 2018, 33: 55-60. PMID: 30567998, PMCID: PMC6317312, DOI: 10.1101/gad.319939.118.Peer-Reviewed Original ResearchConceptsAdhesion genesEpidermal tissue integrityLoss of PRC1PRC1 functionChromatin regulatorsEpigenetic regulationMolecular dissectionPRC2PRC1Gene expressionTissue developmentSkin morphogenesisFunctional linkSkin fragility syndromeEpidermal stratificationEpidermal integrityTissue integrityGenesExpressionH3K27me3Fragility syndromeMorphogenesisRegulatorCobindingRegulationPRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification
Cohen I, Zhao D, Bar C, Valdes VJ, Dauber-Decker KL, Nguyen MB, Nakayama M, Rendl M, Bickmore WA, Koseki H, Zheng D, Ezhkova E. PRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification. Cell Stem Cell 2018, 22: 726-739.e7. PMID: 29727681, PMCID: PMC5944606, DOI: 10.1016/j.stem.2018.04.005.Peer-Reviewed Original ResearchConceptsNon-canonical PRC1 complexesStem cell specificationPRC1 complexesCell specificationSkin developmentDiverse rolesRepressive Complex 1Essential chromatin regulatorsPrecise developmental programExpression of genesCanonical PRC1PRC1 bindsPRC1 functionChromatin regulatorsGene repressionActive genesCell identityRepressor functionDevelopmental programSC formationFurther dissectionGenesPRC2PRC1Function studies
2017
Transcriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress
Zhao D, Mokhtari R, Pedrosa E, Birnbaum R, Zheng D, Lachman HM. Transcriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress. Molecular Autism 2017, 8: 17. PMID: 28367307, PMCID: PMC5372344, DOI: 10.1186/s13229-017-0134-z.Peer-Reviewed Original ResearchConceptsHeat shock protein familyShock protein familyWhole transcriptome analysisChromatin regulatorsAnalysis of microgliaPhenotypic phasesTranscriptome analysisProtein familyRNA-seqCellular stressMethyl-CpGRTT phenotypeRTT pathogenesisDe novo lossGene expressionM2 activation statesFemale miceDifferential expressionFunction mutationsHSP pathwayGenesMolecular pathwaysCell typesExtracellular matrixProtein 2
2016
Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development
Perdigoto CN, Dauber KL, Bar C, Tsai PC, Valdes VJ, Cohen I, Santoriello FJ, Zhao D, Zheng D, Hsu YC, Ezhkova E. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development. PLOS Genetics 2016, 12: e1006151. PMID: 27414999, PMCID: PMC4944976, DOI: 10.1371/journal.pgen.1006151.Peer-Reviewed Original ResearchConceptsMerkel cell specificationCell specificationPrimary hair folliclesLoss of PolycombImportance of ShhCell differentiation programHair follicle functionSonic hedgehog (Shh) signalingPRC2 targetsSpecialized keratinocytesEpidermal progenitorsDevelopmental programHair folliclesEpigenetic processesDifferentiation programHedgehog signalingShh ligandMature Merkel cellsShh signalingSkin developmentMurine dorsal skinEpidermal cellsMerkel cellsPRC2 lossCell formation