2025
The multilayered transcriptional architecture of glioblastoma ecosystems
Nomura M, Spitzer A, Johnson K, Garofano L, Nehar-belaid D, Galili Darnell N, Greenwald A, Bussema L, Oh Y, Varn F, D’Angelo F, Gritsch S, Anderson K, Migliozzi S, Gonzalez Castro L, ChowdhFury T, Robine N, Reeves C, Park J, Lipsa A, Hertel F, Golebiewska A, Niclou S, Nusrat L, Kellet S, Das S, Moon H, Paek S, Bielle F, Laurenge A, Di Stefano A, Mathon B, Picca A, Sanson M, Tanaka S, Saito N, Ashley D, Keir S, Ligon K, Huse J, Yung W, Lasorella A, Verhaak R, Iavarone A, Suvà M, Tirosh I. The multilayered transcriptional architecture of glioblastoma ecosystems. Nature Genetics 2025, 57: 1155-1167. PMID: 40346361, PMCID: PMC12081307, DOI: 10.1038/s41588-025-02167-5.Peer-Reviewed Original ResearchConceptsCell typesSingle-nucleus RNA sequencingDiversity of cellular statesMalignant cell statesGene expression programsTumor DNA sequencingDNA sequencesTranscriptional architectureCellular statesTranscriptional heterogeneityRNA sequencingCell statesCellular heterogeneityExpression programsGenetic aberrationsRecurrent GBM samplesPathway activationLayer of heterogeneityNeuronal-likeNonmalignant cell typesGBM samplesTherapeutic resistanceSequenceEcosystemCell-likeSpecification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines
Scuderi S, Kang T, Jourdon A, Nelson A, Yang L, Wu F, Anderson G, Mariani J, Tomasini L, Sarangi V, Abyzov A, Levchenko A, Vaccarino F. Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines. Cell Stem Cell 2025, 32: 970-989.e11. PMID: 40315847, PMCID: PMC12145255, DOI: 10.1016/j.stem.2025.04.006.Peer-Reviewed Original ResearchConceptsGradient of WntGene expression programsSingle-cell transcriptomicsBrain lineagesMorphogen gradientsEpigenetic variationDorso-ventral axisShh signalingExpression programsMorphogenFetal human brainHuman iPSC linesPluripotent stem cellsCell linesNeuronal lineageNeural tubeShhWntLineagesLine-to-line variationEarly patterningPattern systemPattern variationHuman brain regionsIPSC lines
2024
Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity
Furtado J, Geraldo L, Leser F, Bartkowiak B, Poulet M, Park H, Robinson M, Pibouin-Fragner L, Eichmann A, Boyé K. Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2408674121. PMID: 39693351, PMCID: PMC11670198, DOI: 10.1073/pnas.2408674121.Peer-Reviewed Original ResearchConceptsBlood-retina barrierBlood-retina barrier integrityGene expressionScRNA-seqEndothelial cellsNetrin-1 receptor UNC5BNetrin-1Cell gene expression programsSingle-cell RNA sequencingDevelopment of retinal diseasesWnt signaling componentsGene expression programsTight junction proteinsMutant endothelial cellsScaffold proteinTranscriptional activityLoss of functionRNA sequencingRetinal arteriolesRetina endothelial cellsRetinal diseasesHomologue 1Expression programsReceptor UNC5BEndothelial subtypesEvolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum
Marshall K, Stadtmauer D, Maziarz J, Wagner G, Lesch B. Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum. Developmental Cell 2024, 60: 646-664.e8. PMID: 39536760, PMCID: PMC11859772, DOI: 10.1016/j.devcel.2024.10.013.Peer-Reviewed Original ResearchPlacental mammalsLevel of transcriptionSingle-cell dataGene expression patternsMammalian spermatogenesisGene expression programsEpigenomic dataAdult testisEvolutionary innovationSpermatogenic cellsGene setsSpermatogenic developmentModel marsupialOpossum Monodelphis domesticaGene expressionExpression patternsGenesDevelopmental processesExpression programsSpermatogenesisMonodelphis domesticaMammalsDevelopmental timeCombination of featuresExpressionMechanosensing regulates tissue repair program in macrophages
Meizlish M, Kimura Y, Pope S, Matta R, Kim C, Philip N, Meyaard L, Gonzalez A, Medzhitov R. Mechanosensing regulates tissue repair program in macrophages. Science Advances 2024, 10: eadk6906. PMID: 38478620, PMCID: PMC10936955, DOI: 10.1126/sciadv.adk6906.Peer-Reviewed Original ResearchConceptsExtracellular matrixRegulate chromatin accessibilityTissue repair programGene expression programsCytoskeletal dynamicsChromatin accessibilityAmoeboid migrationCytoskeletal remodelingBiochemical signalsTissue homeostasisExpression programsColony-stimulating factor-1Tissue-resident macrophagesFactor 1MechanosensingRegulating tissue repairTissue integrityMacrophagesTissueThree-dimensional environmentRepair programHomeostasis
2023
Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress
Melnick A, Mullin C, Lin K, McCarter A, Liang S, Liu Y, Wang Q, Jerome N, Choe E, Kunnath N, Bodanapu G, Akter F, Magnuson B, Kumar S, Lombard D, Muntean A, Ljungman M, Sekiguchi J, Ryan R, Chiang M. Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress. Blood 2023, 142: 2159-2174. PMID: 37616559, PMCID: PMC10733839, DOI: 10.1182/blood.2023020144.Peer-Reviewed Original ResearchConceptsT-cell acute lymphoblastic leukemiaNotch signalingActivate transcription of genesExpression programsDNA damageTranscription of genesT-ALL oncogenesTranscription factor ETS1Elevated Notch signalingT-cell leukemia cellsImpaired mitochondrial functionGene expression profilesGene expression programsT cell developmentTranscription machineryActivate transcriptionActivate Notch signalingMitochondrial stressOncogenic NotchTargeting Notch signalingOxidative phosphorylationActivate expressionDNA repairMitochondrial functionNotch complexDistinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages
Wilcox N, Yarovinsky T, Pandya P, Ramgolam V, Moro A, Wu Y, Nicoli S, Hirschi K, Bender J. Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages. IScience 2023, 26: 107985. PMID: 38047075, PMCID: PMC10690575, DOI: 10.1016/j.isci.2023.107985.Peer-Reviewed Original ResearchBone marrow-derived macrophagesTranslation rateAffinity purification assaysGene expression programsTissue-resident macrophagesExpression programsTranscriptional signalsTranslational profilesTranscriptome analysisPosttranscriptional regulationMRNA translationRNA-seqMarrow-derived macrophagesPurification assaysRNA expression levelsProtein HuR.MRNA stabilityDistinct hypoxiaEmbryonic originPotential therapeutic targetTranscriptsExpression levelsAcute perturbationTherapeutic targetIschemic myocardiumTargeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC
Wamsley N, Wilkerson E, Guan L, LaPak K, Schrank T, Holmes B, Sprung R, Gilmore P, Gerndt S, Jackson R, Paniello R, Pipkorn P, Puram S, Rich J, Townsend R, Zevallos J, Zolkind P, Le Q, Goldfarb D, Major M. Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC. Molecular & Cellular Proteomics 2023, 22: 100647. PMID: 37716475, PMCID: PMC10587640, DOI: 10.1016/j.mcpro.2023.100647.Peer-Reviewed Original ResearchConceptsHead and neck squamous cell carcinomaHuman papilloma virus infection statusNeck squamous cell carcinomaProtein expressionT cell infiltrationSquamous cell carcinomaGene expression programsCancer cell modelsSOX2 protein expressionPromote cancer progressionTranscription factorsResponse proteinsPathway componentsMetabolic reprogrammingVirus infection statusCell carcinomaPredictive biomarkersChemoradiation resistanceExpression programsProteomic assaysE7 proteinProtein biomarker assaysImmune evasionPatient stratificationClinical significanceEffector response to necroptotic cell death: an ensemble of immune and stromal cells
Hughes L, Altun O, Nevin J, Wang M, Kluger Y, Pelorosso F, Leighton J, Rothlin C, Ghosh S. Effector response to necroptotic cell death: an ensemble of immune and stromal cells. The Journal Of Immunology 2023, 210: 72.39-72.39. DOI: 10.4049/jimmunol.210.supp.72.39.Peer-Reviewed Original ResearchApoptotic cell deathCell deathGene expression programsEffector responsesNecroptotic cell deathSingle-cell levelMyofibroblast transitionExpression programsStromal cellsTissue renewalTranscriptomic changesCellular corpsesInflammatory bowel diseaseExcessive inflammatory responseInfluence of TGFChemo-genetic approachNon-resolving inflammationMolecular pathwaysResolution of inflammationEssential roleMajor stromal cellsBowel diseaseInflammatory responseInjury modelHelminth infections
2022
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentMicroenvironmental sensing by fibroblasts controls macrophage population size
Zhou X, Franklin RA, Adler M, Carter TS, Condiff E, Adams TS, Pope SD, Philip NH, Meizlish ML, Kaminski N, Medzhitov R. Microenvironmental sensing by fibroblasts controls macrophage population size. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2205360119. PMID: 35930670, PMCID: PMC9371703, DOI: 10.1073/pnas.2205360119.Peer-Reviewed Original ResearchConceptsCell typesDensity-dependent gene expressionTGF-β target genesDiverse cell typesActin-dependent mechanismLineage-specific growth factorsDistinct cell typesGrowth factor availabilityActivation of YAP1Different cell typesExpression programsMicroenvironmental sensingTranscriptional coactivatorTarget genesGene expressionPopulation sizeFactor availabilityPopulation numbersTissue environmentTissue integrityHippoProliferation of macrophagesYAP1Animal tissuesMechanical forcesWithin-host evolution of a gut pathobiont facilitates liver translocation
Yang Y, Nguyen M, Khetrapal V, Sonnert ND, Martin AL, Chen H, Kriegel MA, Palm NW. Within-host evolution of a gut pathobiont facilitates liver translocation. Nature 2022, 607: 563-570. PMID: 35831502, PMCID: PMC9308686, DOI: 10.1038/s41586-022-04949-x.Peer-Reviewed Original ResearchConceptsHost evolutionGene expression programsCell wall structureNon-synonymous mutationsComparative genomicsIndependent lineagesExperimental evolutionExpression programsDivergent evolutionRegulatory genesBacterial behaviorCritical regulatorBacterial translocationGut commensalsTranslocationE. gallinarumMesenteric lymph nodesInitiation of inflammationImmune evasionWall structureEvade DetectionMucosal nicheLactobacillus reuteriCommensalGut microbiotaIntegrating mechanical signals into cellular identity
Carley E, King MC, Guo S. Integrating mechanical signals into cellular identity. Trends In Cell Biology 2022, 32: 669-680. PMID: 35337714, PMCID: PMC9288541, DOI: 10.1016/j.tcb.2022.02.006.Peer-Reviewed Original ResearchConceptsDistinct gene expression programsComplex cellular programsGene expression programsLineage-committed cellsPluripotent stem cellsMulticellular organismsExpression programsCellular identityCellular programsMechanical signalsCell typesStem cellsMechanical inputCellsBiochemical inputsFunction correlationGenomeCytoskeletonOrganismsNumber of studiesImportant determinantComplex axisIdentityLarge arrayVivoGhost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability
Ghosh JC, Perego M, Agarwal E, Bertolini I, Wang Y, Goldman AR, Tang HY, Kossenkov AV, Landis CJ, Languino LR, Plow EF, Morotti A, Ottobrini L, Locatelli M, Speicher DW, Caino MC, Cassel J, Salvino JM, Robert ME, Vaira V, Altieri DC. Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2115624119. PMID: 35177476, PMCID: PMC8872753, DOI: 10.1073/pnas.2115624119.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHumansMitochondriaMitochondrial DynamicsMitochondrial ProteinsMuscle ProteinsNeoplasm InvasivenessNeoplasm MetastasisNeoplasmsNeoplastic ProcessesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesSignal TransductionConceptsEpithelial-mesenchymal transitionGene expression programsTherapeutic vulnerabilitiesTumor cell movementCytokine/chemokine signalingExpression programsTherapeutic targetCell movementMitochondrial dynamicsEssential scaffoldMitochondrial structureSurvival signalingMitochondrial integrityCancer metabolismStress responseActionable therapeutic targetsCell deathChemokine signalingMitochondriaSmall-molecule drug screensCell proliferationOxidative damageInnate immunityMetastatic disseminationHuman tumors
2021
A regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes
Nikhat S, Yadavalli AD, Prusty A, Narayan PK, Palakodeti D, Murre C, Pongubala JMR. A regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2104297118. PMID: 34750254, PMCID: PMC8609617, DOI: 10.1073/pnas.2104297118.Peer-Reviewed Original ResearchConceptsMultipotent progenitorsCell type-specific genesDe novo motif analysisLymphocyte developmentLineage-inappropriate genesHematopoietic multipotent progenitorsSilencing of genesType-specific genesGene expression programsNovo motif analysisEarly T-lymphocyte developmentAlternate cell fatesCell-autonomous mannerGene expression patternsLineage determinantsMyeloid differentiation potentialExpression programsCell fateMiRNAs functionMotif analysisParticular lineageT lymphocyte developmentRegulatory networksLineage commitmentMiRNA targetomeInduction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases
Zheng W, Zhao D, Zhang H, Chinnasamy P, Sibinga N, Pollard JW. Induction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases. Wellcome Open Research 2021, 6: 52. PMID: 33824914, PMCID: PMC8008350, DOI: 10.12688/wellcomeopenres.16569.2.Peer-Reviewed Original ResearchGene expression programsDifferent gene expression profilesGene-targeted mouse modelsGene expression profilesFactor 1Interferon-responsive genesAllograft inflammatory factor-1Metastatic breast cancer cellsExpression programsInflammatory factor-1Functional validationExpression profilesActivated pathwaysMetastatic growthC57BL6/J backgroundBreast cancer cellsSignificant enrichmentFunctional relevanceInterferon SignalingResident alveolar macrophagesBreast cancer metastasisQRT-PCRStrong upregulationCancer metastasisHuman macrophagesTranscriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. European Respiratory Journal 2021, 58: 2002950. PMID: 34083402, PMCID: PMC9759791, DOI: 10.1183/13993003.02950-2020.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisGene co-expression network analysisCo-expression network analysisGene expression programsGene expression patternsDistinct transcriptional programsImmune response pathwaysIon Torrent ProtonMicroarray expression datasetsExpression programsTranscriptional programsPhenotypic traitsGene modulesResponse pathwaysRNA sequencingMolecular endotypesExpression patternsGene expressionHilar lymphadenopathyOrgan involvementGenomic researchMechanistic targetExpression datasetsT helper type 1T cell immune responsesInduction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases
Zheng W, Zhao D, Zhang H, Chinnasamy P, Sibinga N, Pollard J. Induction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases. Wellcome Open Research 2021, 6: 52. DOI: 10.12688/wellcomeopenres.16569.1.Peer-Reviewed Original ResearchGene expression programsDifferent gene expression profilesGene-targeted mouse modelsGene expression profilesFactor 1Interferon-responsive genesAllograft inflammatory factor-1Metastatic breast cancer cellsExpression programsInflammatory factor-1Functional validationExpression profilesActivated pathwaysMetastatic growthC57BL6/J backgroundBreast cancer cellsSignificant enrichmentFunctional relevanceInterferon SignalingResident alveolar macrophagesBreast cancer metastasisQRT-PCRStrong upregulationCancer metastasisHuman macrophagesSingle-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
Muus C, Luecken M, Eraslan G, Sikkema L, Waghray A, Heimberg G, Kobayashi Y, Vaishnav E, Subramanian A, Smillie C, Jagadeesh K, Duong E, Fiskin E, Torlai Triglia E, Ansari M, Cai P, Lin B, Buchanan J, Chen S, Shu J, Haber A, Chung H, Montoro D, Adams T, Aliee H, Allon S, Andrusivova Z, Angelidis I, Ashenberg O, Bassler K, Bécavin C, Benhar I, Bergenstråhle J, Bergenstråhle L, Bolt L, Braun E, Bui L, Callori S, Chaffin M, Chichelnitskiy E, Chiou J, Conlon T, Cuoco M, Cuomo A, Deprez M, Duclos G, Fine D, Fischer D, Ghazanfar S, Gillich A, Giotti B, Gould J, Guo M, Gutierrez A, Habermann A, Harvey T, He P, Hou X, Hu L, Hu Y, Jaiswal A, Ji L, Jiang P, Kapellos T, Kuo C, Larsson L, Leney-Greene M, Lim K, Litviňuková M, Ludwig L, Lukassen S, Luo W, Maatz H, Madissoon E, Mamanova L, Manakongtreecheep K, Leroy S, Mayr C, Mbano I, McAdams A, Nabhan A, Nyquist S, Penland L, Poirion O, Poli S, Qi C, Queen R, Reichart D, Rosas I, Schupp J, Shea C, Shi X, Sinha R, Sit R, Slowikowski K, Slyper M, Smith N, Sountoulidis A, Strunz M, Sullivan T, Sun D, Talavera-López C, Tan P, Tantivit J, Travaglini K, Tucker N, Vernon K, Wadsworth M, Waldman J, Wang X, Xu K, Yan W, Zhao W, Ziegler C. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nature Medicine 2021, 27: 546-559. PMID: 33654293, PMCID: PMC9469728, DOI: 10.1038/s41591-020-01227-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlveolar Epithelial CellsAngiotensin-Converting Enzyme 2Cathepsin LCOVID-19Datasets as TopicDemographyFemaleGene Expression ProfilingHost-Pathogen InteractionsHumansLungMaleMiddle AgedOrgan SpecificityRespiratory SystemSARS-CoV-2Sequence Analysis, RNASerine EndopeptidasesSingle-Cell AnalysisVirus InternalizationConceptsSingle-cell RNA-sequencing studiesRNA-sequencing studiesSpecific expression patternsExpression programsKey immune functionsExpression patternsSARS-CoV-2 entry genesSpecific expressionAlveolar type 2 cellsMolecular pathwaysLung parenchyma samplesCoronavirus disease 2019 (COVID-19) transmissionDifferent tissuesCellular entryGenesRespiratory epithelial cellsAirway secretory cellsSecretory cellsTumor necrosis factorEntry genesExpression levelsType 2 cellsEpithelial cellsGut tissueSpecific subsetAnnotation of chromatin states in 66 complete mouse epigenomes during development
van der Velde A, Fan K, Tsuji J, Moore J, Purcaro M, Pratt H, Weng Z. Annotation of chromatin states in 66 complete mouse epigenomes during development. Communications Biology 2021, 4: 239. PMID: 33619351, PMCID: PMC7900196, DOI: 10.1038/s42003-021-01756-4.Peer-Reviewed Original ResearchConceptsChromatin stateMouse epigenomesPolycomb repressive complex proteinsBivalent chromatin stateTranscription start siteRepressive mark H3K27me3Silence target genesCharacteristics of promotersChromHMM algorithmUnique epigenomeGene expression programsENCODE projectTranscribed regionsMulticellular organismsStart siteRepressed regionsActive marksMammalian developmentComplex proteinsEpigenomeTissue specificityTarget genesExpression programsCell typesIntegrated analysis
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