2025
Suppression of Autosomal Dominant Polycystic Kidney Disease Influences Epithelial Cell Transcription Program
Rai V, Failli M, Fiusco M, Reyna-Neyra A, Onuchic L, di Bernardo D, Craft J, Caplan M. Suppression of Autosomal Dominant Polycystic Kidney Disease Influences Epithelial Cell Transcription Program. Physiology 2025, 40: 0966. DOI: 10.1152/physiol.2025.40.s1.0966.Peer-Reviewed Original ResearchC-terminal tailCystic phenotypeTranscriptional programsAutosomal dominant polycystic kidney diseaseScRNA-seqTranscriptional differencesAmino acid C-terminal tailAcidic C-terminal tailPolycystin-1 proteinCell transcriptional programDifferentiated cell stateEpithelial cellsSingle cell RNA sequencingDoxycycline-inducible mouse modelCell RNA sequencingNovel transcriptsLibrary preparationCell transcriptional profilingChromium technologyPKD1 geneBiological replicatesRNA velocityCDNA synthesisRNA sequencingTranscriptional profiles
2024
Transcriptional regulation of postnatal aortic development
Weiss D, Yeung N, Ramachandra A, Humphrey J. Transcriptional regulation of postnatal aortic development. Cells And Development 2024, 180: 203971. PMID: 39426523, PMCID: PMC11634634, DOI: 10.1016/j.cdev.2024.203971.Peer-Reviewed Original ResearchDistinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.
Verma S, Bradley M, Gray J, Dogra P, Caron D, Maurrasse S, Grunstein E, Waldman E, Jang M, Pethe K, Farber D, Connors T. Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells. The Journal Of Immunology 2024, 213: 306-316. PMID: 38905110, PMCID: PMC11304551, DOI: 10.4049/jimmunol.2300890.Peer-Reviewed Original ResearchRegulatory T cellsT cellsTreg biologyCD4+ regulatory T cellsCD8+ T cellsIncreased Foxp3 expressionProportion of TregsProduction of IL-10Paired blood samplesHigher proliferative capacityTranscriptional profilesAdult TregsTreg activityFoxp3 expressionTreg identityExtrafollicular regionsTregsIL-10Primary siteProtective immunityProliferative capacityImmune responseImmunological developmentAdult subjectsImmune systemTranscriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes
Lu X, Ni P, Suarez-Meade P, Ma Y, Forrest E, Wang G, Wang Y, Quiñones-Hinojosa A, Gerstein M, Jiang Y. Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes. Cell Reports 2024, 43: 114376. PMID: 38900637, PMCID: PMC11328446, DOI: 10.1016/j.celrep.2024.114376.Peer-Reviewed Original ResearchSHANK family genesFamily genesLong-read sequencingCDNA captureTranscript structureDeleterious variantsGenomic studiesAbundant mRNAsTranscriptional dysregulationStochastic transcriptionStudies of neuropsychiatric disordersCausative genesTranscriptional profilesTranscriptional determinantsTranscriptomePostmortem brain tissueAutism spectrum disorderShank3 transcriptsTranscriptionGenesGenomeSHANK3Neuropsychiatric disordersSpectrum disorderAutism modelEzrin drives adaptation of monocytes to the inflamed lung microenvironment.
Gudneppanavar R, Di Pietro C, Oez H, Zhang P, Huang P, Braga C, Tebaldi T, Biancon G, Kim C, Gonzalez A, Halene S, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. The Journal Of Immunology 2024, 212: 0078_5418-0078_5418. DOI: 10.4049/jimmunol.212.supp.0078.5418.Peer-Reviewed Original ResearchRNA-seqActin-binding protein ezrinF-actin distributionImmune response to bacteriaCystic fibrosisIn vitro functional studiesResponse to bacteriaIncreased expression of pro-inflammatory markersCytoskeleton rearrangementF-actinResponse to lung infectionExpressed genesProtein ezrinTranscriptional profilesExpression of pro-inflammatory markersPlasma membranePro-inflammatory markersFunctional studiesEzrinLung extracellular matrixCF miceExtracellular matrixWT micePI3K/Akt signalingLung infectionIdentification of Early Transcriptional Markers of Autosomal Dominant Polycystic Kidney Disease Cystic Epithelial Cells
Rai V, Failli M, Fiusco M, Reyna-Neyra A, di Bernardo D, Craft J, Caplan M. Identification of Early Transcriptional Markers of Autosomal Dominant Polycystic Kidney Disease Cystic Epithelial Cells. Physiology 2024, 39: 1176. DOI: 10.1152/physiol.2024.39.s1.1176.Peer-Reviewed Original ResearchC-terminal tailAutosomal dominant polycystic kidney diseaseScRNA-seqPolycystin-1 C-terminal tailPolycystin-1 proteinEpithelial cellsSingle cell RNA sequencingTranscriptional signatureCell RNA sequencingLibrary preparationChromium technologyCystic epithelial cellsBiological replicatesPolycystin-1Amino acid portionTranscriptional programsCDNA synthesisRNA sequencingTranscriptional changesTranscriptional profilesCyst epithelial cellsExpression of multiple markersMonogenic diseasesDominant polycystic kidney diseaseProtein expression levelsLytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells
Zamora P, Reidy T, Armbruster C, Sun M, Van Tyne D, Turner P, Koff J, Bomberger J. Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells. PLOS Biology 2024, 22: e3002566. PMID: 38652717, PMCID: PMC11037538, DOI: 10.1371/journal.pbio.3002566.Peer-Reviewed Original ResearchConceptsLytic phagesLytic bacteriophagesPhage therapyAirway epithelial cellsPseudomonas aeruginosa phagesEpithelial cellsMultidrug resistanceAirway epitheliumCystic fibrosisProinflammatory cytokinesHuman respiratory epithelial cellsPhage exposurePhage familiesMammalian cell responsesHuman airway epithelial cellsInternalized phageTreat multidrug-resistantPhageBacterial isolatesTranscriptional profilesRespiratory epithelial cellsHuman hostChronic respiratory disordersBacterial biofilmsBacteriophage
2023
Normalizing need not be the norm: count-based math for analyzing single-cell data
Church S, Mah J, Wagner G, Dunn C. Normalizing need not be the norm: count-based math for analyzing single-cell data. Theory In Biosciences 2023, 143: 45-62. PMID: 37947999, DOI: 10.1007/s12064-023-00408-x.Peer-Reviewed Original ResearchThree Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients
Makinde H, Dunn JLM, Gadhvi G, Carns M, Aren K, Chung AH, Muhammad LN, Song J, Cuda CM, Dominguez S, Pandolfino JE, D'Amico J, Budinger GS, Assassi S, Frech TM, Khanna D, Shaeffer A, Perlman H, Hinchcliff M, Winter DR. Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients. Arthritis & Rheumatology 2023, 75: 595-608. PMID: 36281773, PMCID: PMC10165944, DOI: 10.1002/art.42380.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisNonclassical monocytesClassical monocytesSSc patientsTranscriptional signatureSystemic sclerosisSkin diseasesCharacteristic transcriptional signaturesRNA-seq dataSSc skin diseaseWorse lung functionCutaneous systemic sclerosisEarly systemic sclerosisActivity outcome measuresDistinct transcriptional profilesTranscriptional profilingRNA sequencingTranscriptional profilesProspective registryDisease activityLung functionComplex clinical phenotypeGene expressionPeripheral bloodMinority cell population
2022
Benchmarking transcriptional host response signatures for infection diagnosis
Chawla D, Cappuccio A, Tamminga A, Sealfon S, Zaslavsky E, Kleinstein S. Benchmarking transcriptional host response signatures for infection diagnosis. Cell Systems 2022, 13: 974-988.e7. PMID: 36549274, PMCID: PMC9768893, DOI: 10.1016/j.cels.2022.11.007.Peer-Reviewed Original ResearchConceptsInfection diagnosisHost response signatureNon-infectious conditionsClinical applicationResponse signatureChronic infectionPathogen of interestBacterial infectionsInfectionSignature of infectionDisease signaturesDiagnosisTranscriptional profilesStandardized methodologyDevelopment of signaturesDecreased performancePan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvantDifferential Expression of Cell Wall Remodeling Genes Is Part of the Dynamic Phase-Specific Transcriptional Program of Conidial Germination of Trichoderma asperelloides
Gortikov M, Yakubovich E, Wang Z, López-Giráldez F, Tu Y, Townsend JP, Yarden O. Differential Expression of Cell Wall Remodeling Genes Is Part of the Dynamic Phase-Specific Transcriptional Program of Conidial Germination of Trichoderma asperelloides. Journal Of Fungi 2022, 8: 854. PMID: 36012842, PMCID: PMC9410309, DOI: 10.3390/jof8080854.Peer-Reviewed Original ResearchPolar growthTranscript abundanceConidial germinationGlucanase-encoding geneOnset of germinationTranscriptional hubsTranscriptional programsTrichoderma asperelloidesHyphal growthTranscriptional profilesDevelopmental eventsChitin synthaseHost recognitionDifferential expressionGerminationSpecific membersDormant conidiaFirst branchingGenomeGenesInitial branchingAbundanceNetwork analysisExpressionMorphological progressionDissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain
Marsh SE, Walker AJ, Kamath T, Dissing-Olesen L, Hammond TR, de Soysa TY, Young AMH, Murphy S, Abdulraouf A, Nadaf N, Dufort C, Walker AC, Lucca LE, Kozareva V, Vanderburg C, Hong S, Bulstrode H, Hutchinson PJ, Gaffney DJ, Hafler DA, Franklin RJM, Macosko EZ, Stevens B. Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain. Nature Neuroscience 2022, 25: 306-316. PMID: 35260865, PMCID: PMC11645269, DOI: 10.1038/s41593-022-01022-8.Peer-Reviewed Original ResearchConceptsSingle-cell sequencing experimentsCell type diversitySingle-cell sequencingRNA-sequencing datasetsGene expression changesGene expression signaturesVivo gene expressionTranscriptional profilesGene expressionExpression changesSequencing experimentsGlial signaturesDownstream analysisExpression signaturesTissue typesSingle cell suspensionsOptimal cell yieldIntact tissueHuman tissuesCell yieldEnzymatic dissociationHuman samplesTissue digestionPostmortem human samplesTissue
2021
Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture
Lu Y, Liu M, Yang J, Weissman SM, Pan X, Katz SG, Wang S. Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture. Cell Discovery 2021, 7: 47. PMID: 34183665, PMCID: PMC8238952, DOI: 10.1038/s41421-021-00266-1.Peer-Reviewed Original ResearchWild typeCell typesHSC nicheMultiplexed error-robust fluorescenceStem cell niche architectureFetal liverHematopoietic stem cell nicheStem cell nicheLoss of TET2Endothelial cellsBioinformatic foundationNumber of HSCsNiche architectureTranscriptome profilingSpatial regulationTranscriptional profilesCell nicheArterial endothelial cellsIndividual cellsNicheSitu hybridizationSpatial organizationLiver cell typesMicroenvironment regulationRobust fluorescence
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytesHeterogeneity of midgut cells and their differential responses to blood meal ingestion by the mosquito, Aedes aegypti
Cui Y, Franz AWE. Heterogeneity of midgut cells and their differential responses to blood meal ingestion by the mosquito, Aedes aegypti. Insect Biochemistry And Molecular Biology 2020, 127: 103496. PMID: 33188922, PMCID: PMC7739889, DOI: 10.1016/j.ibmb.2020.103496.Peer-Reviewed Original ResearchConceptsIntestinal stem cellsBlood meal ingestionMosquito midgutSingle-nucleus RNA sequencingCell type clustersCell typesVisceral muscle cellsNutrient absorptionCell type compositionHuman pathogenic parasitesNumerous mosquito speciesEC-like cellsBlood meal digestionEnteroendocrine cellsAedes aegyptiBlood-feeding behaviorMeal ingestionCellular homeostasisCellular diversityGenetic compatibilityHematophagous insectsFemale midgutTranscriptional profilesBlood digestionRNA sequencingGene X environment: the cellular environment governs the transcriptional response to environmental chemicals
Burman A, Garcia-Milian R, Whirledge S. Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals. Human Genomics 2020, 14: 19. PMID: 32448403, PMCID: PMC7247264, DOI: 10.1186/s40246-020-00269-1.Peer-Reviewed Original ResearchConceptsTranscriptional responseCellular environmentCellular contextGenetic sexUnique gene networksGene regulatory networksEnvironment interactionEnvironmental chemicalsGene expression studiesUnique transcriptional profileGene expression array dataExpression array dataPhenotype of cellsGene networksRegulatory networksTranscriptional profilesBiological functionsCellular organizationExpression studiesFemale cellsCellular responsesPhysiological cuesHuman gene expression studiesMolecular pathwaysGenetic resultsASCL1- and DLX2-induced GABAergic neurons from hiPSC-derived NPCs
Barretto N, Zhang H, Powell SK, Fernando MB, Zhang S, Flaherty EK, Ho SM, Slesinger PA, Duan J, Brennand KJ. ASCL1- and DLX2-induced GABAergic neurons from hiPSC-derived NPCs. Journal Of Neuroscience Methods 2020, 334: 108548. PMID: 32065989, PMCID: PMC7426253, DOI: 10.1016/j.jneumeth.2019.108548.Peer-Reviewed Original ResearchNeural progenitor cellsHiPSC-NPCsSomatic cell reprogrammingGABAergic neuronsHiPSC-derived neural progenitor cellsDifferentiation of hiPSCsDistinct transcriptional profilesPluripotent stem cellsCell reprogrammingPatient-derived cellsElectrophysiological maturityFunctional GABAergic neuronsTranscriptional profilesNeuronal inductionStem cellsProgenitor cellsLentiviral overexpressionPure populationsDlx2Study of diseasesAscl1HiPSCsNeuronal populationsInduction protocolCell source
2019
Prefrontal cortex interneurons display dynamic sex-specific stress-induced transcriptomes
Girgenti MJ, Wohleb ES, Mehta S, Ghosal S, Fogaca MV, Duman RS. Prefrontal cortex interneurons display dynamic sex-specific stress-induced transcriptomes. Translational Psychiatry 2019, 9: 292. PMID: 31712551, PMCID: PMC6848179, DOI: 10.1038/s41398-019-0642-z.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingInitiation factor 2Distinct transcriptome profilesTranslational machineryTranscriptome profilesEnriched pathwaysTranscriptional pathwaysTranscriptional profilesRNA sequencingDepressive-like behaviorSST interneuronsKey pathwaysChronic stressInterneuron subtypesSex-specific differencesPrefrontal cortexCell sortingSignificant dysregulationFactor 2PathwayStress-induced depressive-like behaviorDecreased expressionReporter miceGrowth factorNon-stressed femalesSpecific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice
Wang A, Pope SD, Weinstein JS, Yu S, Zhang C, Booth CJ, Medzhitov R. Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 2200-2209. PMID: 30674681, PMCID: PMC6369774, DOI: 10.1073/pnas.1820704116.Peer-Reviewed Original ResearchConceptsSecondary hemophagocytic lymphohistiocytosisAssociated transcriptional programRNA sequencing analysisBone marrow-derived macrophagesTranscriptional programsTranscriptional profilingMarrow-derived macrophagesBone marrow macrophagesTranscriptional profilesNonlethal doseMitochondrial functionToll-like receptor agonistsSequencing analysisSpecific sequencesSetting of infectionGlycolytic metabolismMarrow macrophagesUseful therapeutic strategyGlycolysis inhibitorLethal stateHyperinflammatory stateHyperinflammatory responseOxidative metabolismHemophagocytic lymphohistiocytosisMortal complications
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