2024
Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression
Hodgson L, Li Y, Iturria-Medina Y, Stratton J, Wolf G, Krishnaswamy S, Bennett D, Bzdok D. Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression. Communications Biology 2024, 7: 591. PMID: 38760483, PMCID: PMC11101463, DOI: 10.1038/s42003-024-06273-8.Peer-Reviewed Original ResearchConceptsGene programAlzheimer's diseaseLate-onset Alzheimer's diseaseAD risk lociCell type-specificSingle-nucleus RNA sequencingRisk lociAD brainAlzheimer's disease progressionSnRNA-seqRNA sequencingAD pathophysiologySignaling cascadesTranscriptome modulationProgressive neurodegenerative diseaseCell-typeGWASNeurodegenerative diseasesNeuronal lossGlial cellsTranscriptomeLociGenesPseudo-trajectoriesDisease progressionParasympathetic neurons derived from human pluripotent stem cells model human diseases and development
Wu H, Saito-Diaz K, Huang C, McAlpine J, Seo D, Magruder D, Ishan M, Bergeron H, Delaney W, Santori F, Krishnaswamy S, Hart G, Chen Y, Hogan R, Liu H, Ivanova N, Zeltner N. Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development. Cell Stem Cell 2024, 31: 734-753.e8. PMID: 38608707, PMCID: PMC11069445, DOI: 10.1016/j.stem.2024.03.011.Peer-Reviewed Original ResearchConceptsAutonomic nervous systemSjogren's syndromeParasympathetic neuronsFamilial dysautonomiaWhite adipocytesAutoimmune disease Sjogren's syndromeHuman pluripotent stem cellsHuman pluripotent stem cell (hPSC)-derived neuronsHuman developmental studiesPluripotent stem cellsSARS-CoV-2 infectionSchwann cell progenitorsAutonomic neuropathyCell progenitorsStem cellsModel systemNervous systemSARS-CoV-2Human diseasesDysfunctionNeuronsDifferentiation paradigmOrgan developmentNeuropathyDrug discovery studies
2023
Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses
Ramos Zapatero M, Tong A, Opzoomer J, O'Sullivan R, Cardoso Rodriguez F, Sufi J, Vlckova P, Nattress C, Qin X, Claus J, Hochhauser D, Krishnaswamy S, Tape C. Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses. Cell 2023, 186: 5606-5619.e24. PMID: 38065081, DOI: 10.1016/j.cell.2023.11.005.Peer-Reviewed Original ResearchPD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin toleranceMultiscale geometric and topological analyses for characterizing and predicting immune responses from single cell data
Venkat A, Bhaskar D, Krishnaswamy S. Multiscale geometric and topological analyses for characterizing and predicting immune responses from single cell data. Trends In Immunology 2023, 44: 551-563. PMID: 37301677, DOI: 10.1016/j.it.2023.05.003.Peer-Reviewed Original ResearchHSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal
Pierce C, Loh L, Steach H, Cheshenko N, Preston-Hurlburt P, Zhang F, Stransky S, Kravets L, Sidoli S, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal. Journal Of Clinical Investigation 2023, 133: e164317. PMID: 37079384, PMCID: PMC10232005, DOI: 10.1172/jci164317.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV latency reversalT cellsLatency reversalHuman CD4HIV-1 viral loadHIV-1 restriction factorsHSV-2 recurrencesHSV-2 infectionHIV-1 latencyUpregulation of MALAT1Primary human CD4HSV-2 proteinsViral loadHIV replicationPeripheral bloodMALAT1 expressionHSV-2Tissue reservoirsCD4Viral replicationExpression of transcriptsBystander cellsRestriction factorsMALAT1linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells
Tornini V, Miao L, Lee H, Gerson T, Dube S, Schmidt V, Kroll F, Tang Y, Du K, Kuchroo M, Vejnar C, Bazzini A, Krishnaswamy S, Rihel J, Giraldez A. linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells. ELife 2023, 12: e82249. PMID: 37191016, PMCID: PMC10188112, DOI: 10.7554/elife.82249.Peer-Reviewed Original ResearchConceptsCell typesIntergenic non-coding RNAsChromatin architectural proteinCryptic open reading frameGene regulatory networksOpen reading frameNon-coding RNAsNew cell typesNeural cell typesBrain cell typesPutative lincRNAsVertebrate genomesArchitectural proteinsChromatin disruptionChromatin accessibilityRegulatory networksGenetic basisCell developmentMicropeptidesBrain cell developmentReceptor-mediated pathwaySystematic identificationLincRNAsNeural cellsCerebellar cellsSingle-cell analysis reveals inflammatory interactions driving macular degeneration
Kuchroo M, DiStasio M, Song E, Calapkulu E, Zhang L, Ige M, Sheth A, Majdoubi A, Menon M, Tong A, Godavarthi A, Xing Y, Gigante S, Steach H, Huang J, Huguet G, Narain J, You K, Mourgkos G, Dhodapkar R, Hirn M, Rieck B, Wolf G, Krishnaswamy S, Hafler B. Single-cell analysis reveals inflammatory interactions driving macular degeneration. Nature Communications 2023, 14: 2589. PMID: 37147305, PMCID: PMC10162998, DOI: 10.1038/s41467-023-37025-7.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationMacular degenerationNeurodegenerative diseasesNeurodegenerative conditionsLate-stage age-related macular degenerationPossible new therapeutic targetsPostmortem human retinaProgressive multiple sclerosisNew therapeutic targetsEarly phaseSingle-nucleus RNA sequencingInflammatory interactionsMultiple sclerosisInterleukin-1βDisease progressionControl retinasTherapeutic approachesGlial populationsGlial stateTherapeutic targetDisease pathogenesisRetinal diseasesAlzheimer's diseaseDiseaseHuman retinaIntegrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations
Ren J, Qu R, Rahman N, Lewis J, King A, Liao X, Mirza F, Carlson K, Huang Y, Gigante S, Evans B, Rajendran B, Xu S, Wang G, Foss F, Damsky W, Kluger Y, Krishnaswamy S, Girardi M. Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations. Blood Advances 2023, 7: 445-457. PMID: 35947128, PMCID: PMC9979716, DOI: 10.1182/bloodadvances.2022008168.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaMalignant CTCL cellsDiverse transcriptomic profilesT cellsSingle-cell RNACTCL cellsDevelopment of CTCLIntegrated transcriptomeT-cell receptor sequencingT cell exhaustion phenotypeCommon antigenic stimulusPeripheral blood CD4Transcriptomic profilesGene expressionT-cell lymphomaIntegrative analysisPotential therapeutic targetProliferation advantageLimited diversityBlood CD4Blood involvementMutation levelsExhaustion phenotypeWorse prognosisAntigenic stimulus
2022
Multiscale PHATE identifies multimodal signatures of COVID-19
Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingTransposase-accessible chromatinSingle-cell sequencingRNA sequencingBiological insightsPopulation groupingsSophisticated computational toolsBiological featuresSequencingFlow cytometryComputational toolsChromatinBiomedical communityDifferent data typesCell responsesCellsPhate
2013
viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia
Amir el-AD, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, Shenfeld DK, Krishnaswamy S, Nolan GP, Pe'er D. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nature Biotechnology 2013, 31: 545-552. PMID: 23685480, PMCID: PMC4076922, DOI: 10.1038/nbt.2594.Peer-Reviewed Original Research