2023
Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1
Tejwani L, Ravindra N, Lee C, Cheng Y, Nguyen B, Luttik K, Ni L, Zhang S, Morrison L, Gionco J, Xiang Y, Yoon J, Ro H, Haidery F, Grijalva R, Bae E, Kim K, Martuscello R, Orr H, Zoghbi H, McLoughlin H, Ranum L, Shakkottai V, Faust P, Wang S, van Dijk D, Lim J. Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1. Neuron 2023, 112: 362-383.e15. PMID: 38016472, PMCID: PMC10922326, DOI: 10.1016/j.neuron.2023.10.039.Peer-Reviewed Original ResearchRegulation of gene editing using T-DNA concatenation
Dickinson L, Yuan W, LeBlanc C, Thomson G, Wang S, Jacob Y. Regulation of gene editing using T-DNA concatenation. Nature Plants 2023, 9: 1398-1408. PMID: 37653336, PMCID: PMC11193869, DOI: 10.1038/s41477-023-01495-w.Peer-Reviewed Original ResearchConceptsT-DNA copy numberLong terminal repeatGene editingCopy numberT-DNA copiesPlant gene editingT-DNA structureTransfer DNAT-DNADNA repeatsAgrobacterium tumefaciensDNA repairSingle copyGene targetingExogenous DNATerminal repeatMolecular determinantsArabidopsisLarge concatemersRepeatsDNAEditingCopiesRad17RetrotransposonsFemale naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations
Patterson B, Yang B, Tanaka Y, Kim K, Cakir B, Xiang Y, Kim J, Wang S, Park I. Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations. Science Advances 2023, 9: eadf2245. PMID: 37540754, PMCID: PMC10403202, DOI: 10.1126/sciadv.adf2245.Peer-Reviewed Original ResearchConceptsNaïve human pluripotent stem cellsHuman pluripotent stem cellsX-chromosome inactivationX chromosomePluripotent stem cellsStem cellsNaïve human embryonic stem cellsX chromosome stateX chromosome statusInactive X chromosomeActive X chromosomeHuman embryonic stem cellsEarly embryonic cellsEmbryonic stem cellsUnique epigenetic regulationChromatin compactionGenomic resolutionEpigenetic regulationChromosome inactivationChromosome stateSomatic cellsEmbryonic cellsChromosomesChromosome statusCellsAn integrated platform for high-throughput nanoscopy
Barentine A, Lin Y, Courvan E, Kidd P, Liu M, Balduf L, Phan T, Rivera-Molina F, Grace M, Marin Z, Lessard M, Rios Chen J, Wang S, Neugebauer K, Bewersdorf J, Baddeley D. An integrated platform for high-throughput nanoscopy. Nature Biotechnology 2023, 41: 1549-1556. PMID: 36914886, PMCID: PMC10497732, DOI: 10.1038/s41587-023-01702-1.Peer-Reviewed Original ResearchConceptsLarge data volumesUser-defined extensionsPlugin frameworkData compressionData volumeCamera frameFrame rateAnalysis platformAcquisition taskPlatformIntegrated acquisitionThroughputSingle-molecule localization microscopyTypical throughputHundreds of cellsThree-dimensional fluorescenceFrameworkTens of cellsLocalization microscopyWorkflowLive imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo
May D, Yun S, Gonzalez D, Park S, Chen Y, Lathrop E, Cai B, Xin T, Zhao H, Wang S, Gonzalez L, Cockburn K, Greco V. Live imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo. ELife 2023, 12: e83444. PMID: 36880644, PMCID: PMC10027315, DOI: 10.7554/elife.83444.Peer-Reviewed Original ResearchConceptsStem cell differentiationCell differentiationStem cell compartmentCompaction changesChromatin compaction statesDynamic transcriptional statesCell compartmentChromatin architectureCell cycle statusChromatin rearrangementNascent RNATranscriptional burstingTranscriptional statesLive imagingTissue contextGene expressionDifferentiating cellsGlobal remodelingIndividual cellsCycle statusStem cellsDifferentiation statusDifferentiationCellsMorphological changes
2022
NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health
Lee P, Benz C, Blood P, Börner K, Campisi J, Chen F, Daldrup-Link H, De Jager P, Ding L, Duncan F, Eickelberg O, Fan R, Finkel T, Furman D, Garovic V, Gehlenborg N, Glass C, Heckenbach I, Joseph Z, Katiyar P, Kim S, Königshoff M, Kuchel G, Lee H, Lee J, Ma J, Ma Q, Melov S, Metis K, Mora A, Musi N, Neretti N, Passos J, Rahman I, Rivera-Mulia J, Robson P, Rojas M, Roy A, Scheibye-Knudsen M, Schilling B, Shi P, Silverstein J, Suryadevara V, Xie J, Wang J, Wong A, Niedernhofer L, Wang S, Anvari H, Balough J, Benz C, Bons J, Brenerman B, Evans W, Gerencser A, Gregory H, Hansen M, Justice J, Kapahi P, Murad N, O’Broin A, Pavone M, Powell M, Scott G, Shanes E, Shankaran M, Verdin E, Winer D, Wu F, Adams A, Blood P, Bueckle A, Cao-Berg I, Chen H, Davis M, Filus S, Hao Y, Hartman A, Hasanaj E, Helfer J, Herr B, Joseph Z, Molla G, Mou G, Puerto J, Quardokus E, Ropelewski A, Ruffalo M, Satija R, Schwenk M, Scibek R, Shirey W, Sibilla M, Welling J, Yuan Z, Bonneau R, Christiano A, Izar B, Menon V, Owens D, Phatnani H, Smith C, Suh Y, Teich A, Bekker V, Chan C, Coutavas E, Hartwig M, Ji Z, Nixon A, Dou Z, Rajagopal J, Slavov N, Holmes D, Jurk D, Kirkland J, Lagnado A, Tchkonia T, Abraham K, Dibattista A, Fridell Y, Howcroft T, Jhappan C, Montes V, Prabhudas M, Resat H, Taylor V, Kumar M, Suryadevara V, Cigarroa F, Cohn R, Cortes T, Courtois E, Chuang J, Davé M, Domanskyi S, Enninga E, Eryilmaz G, Espinoza S, Gelfond J, Kirkland J, Kuchel G, Kuo C, Lehman J, Aguayo-Mazzucato C, Meves A, Rani M, Sanders S, Thibodeau A, Tullius S, Ucar D, White B, Wu Q, Xu M, Yamaguchi S, Assarzadegan N, Cho C, Hwang I, Hwang Y, Xi J, Adeyi O, Aliferis C, Bartolomucci A, Dong X, DuFresne-To M, Ikramuddin S, Johnson S, Nelson A, Niedernhofer L, Revelo X, Trevilla-Garcia C, Sedivy J, Thompson E, Robbins P, Wang J, Aird K, Alder J, Beaulieu D, Bueno M, Calyeca J, Chamucero-Millaris J, Chan S, Chung D, Corbett A, Gorbunova V, Gowdy K, Gurkar A, Horowitz J, Hu Q, Kaur G, Khaliullin T, Lafyatis R, Lanna S, Li D, Ma A, Morris A, Muthumalage T, Peters V, Pryhuber G, Reader B, Rosas L, Sembrat J, Shaikh S, Shi H, Stacey S, Croix C, Wang C, Wang Q, Watts A, Gu L, Lin Y, Rabinovitch P, Sweetwyne M, Artyomov M, Ballentine S, Chheda M, Davies S, DiPersio J, Fields R, Fitzpatrick J, Fulton R, Imai S, Jain S, Ju T, Kushnir V, Link D, Ben Major M, Oh S, Rapp D, Rettig M, Stewart S, Veis D, Vij K, Wendl M, Wyczalkowski M, Craft J, Enninful A, Farzad N, Gershkovich P, Halene S, Kluger Y, VanOudenhove J, Xu M, Yang J, Yang M. NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. Nature Aging 2022, 2: 1090-1100. PMID: 36936385, PMCID: PMC10019484, DOI: 10.1038/s43587-022-00326-5.Peer-Reviewed Original ResearchConceptsSenescence-associated secretory phenotypeSenescent cellsSecretory phenotypeMulti-omics datasetsStable growth arrestHuman lifespanDiverse rolesGrowth arrestProinflammatory senescence-associated secretory phenotypeHuman tissuesPhenotypeMetabolic changesCellsHuman healthLifespanPhysiological healthCommon Coordinate FrameworkNew mechanism of chromatin compartmentalization by BRD2
Cheng Y, Wang S. New mechanism of chromatin compartmentalization by BRD2. Trends In Genetics 2022, 38: 1197-1198. PMID: 35811175, DOI: 10.1016/j.tig.2022.06.016.Peer-Reviewed Original Research
2021
TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng Y, Liu M, Hu M, Wang S. TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations. Genome Biology 2021, 22: 309. PMID: 34749781, PMCID: PMC8574027, DOI: 10.1186/s13059-021-02523-8.Peer-Reviewed Original ResearchConceptsInactive X chromosomeActive X chromosomeMajor epigenetic componentsSingle-cell domainsX chromosomeEpigenetic componentsThree-dimensional genome architectureGlobal epigenetic landscapeFemale human cellsLoop extrusion mechanismSame genomic regionGenome architectureChromatin domainsTAD structureChromatin compactionEpigenetic landscapeTAD boundariesChromatin foldingGenomic regionsChromosome copiesGenomic techniquesEpigenetic perturbationsEpigenetic interactionsDistinct cell linesChromosomesSpatial 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 fluorescenceChromatin tracing and multiplexed imaging of nucleome architectures (MINA) and RNAs in single mammalian cells and tissue
Liu M, Yang B, Hu M, Radda JSD, Chen Y, Jin S, Cheng Y, Wang S. Chromatin tracing and multiplexed imaging of nucleome architectures (MINA) and RNAs in single mammalian cells and tissue. Nature Protocols 2021, 16: 2667-2697. PMID: 33903756, PMCID: PMC9007104, DOI: 10.1038/s41596-021-00518-0.Peer-Reviewed Original ResearchConceptsSame single cellNucleome architecturesGene expressionMammalian tissuesChromatin foldingNuclear laminaSingle cellsNumerous RNA speciesDifferent biological processesSingle mammalian cellsDifferent cell typesMultiplexed imagingGenomic organizationGenomic architectureChromatin loopsGenomic regionsRNA speciesIndividual chromosomesMammalian cellsGenomic techniquesBiological processesDetailed protocolCopy numberCell typesNormal development
2020
ProbeDealer is a convenient tool for designing probes for highly multiplexed fluorescence in situ hybridization
Hu M, Yang B, Cheng Y, Radda JSD, Chen Y, Liu M, Wang S. ProbeDealer is a convenient tool for designing probes for highly multiplexed fluorescence in situ hybridization. Scientific Reports 2020, 10: 22031. PMID: 33328483, PMCID: PMC7745008, DOI: 10.1038/s41598-020-76439-x.Peer-Reviewed Original ResearchConceptsSingle-molecule RNA FISHSpecific genomic lociSitu hybridizationNucleome architecturesRNA FISHGenomic lociRNA speciesMultiplexed fluorescenceFISH techniqueFishRecent technological advancesMultiplexed imagingHybridizationMultiplexed mannerLociSpeciesFluorescencePowerful methodNotable exampleProbeProbe designTechnological advancesChromatin Tracing: Imaging 3D Genome and Nucleome
Hu M, Wang S. Chromatin Tracing: Imaging 3D Genome and Nucleome. Trends In Cell Biology 2020, 31: 5-8. PMID: 33191055, PMCID: PMC8094612, DOI: 10.1016/j.tcb.2020.10.006.Peer-Reviewed Original ResearchMultiplexed imaging of nucleome architectures in single cells of mammalian tissue
Liu M, Lu Y, Yang B, Chen Y, Radda JSD, Hu M, Katz SG, Wang S. Multiplexed imaging of nucleome architectures in single cells of mammalian tissue. Nature Communications 2020, 11: 2907. PMID: 32518300, PMCID: PMC7283333, DOI: 10.1038/s41467-020-16732-5.Peer-Reviewed Original ResearchConceptsNucleome architecturesChromatin organizationMammalian tissuesNumerous RNA speciesNumerous genomic regionsSpecific chromatin architectureSurface of chromosomesSingle cellsDifferent cell typesMouse fetal liverChromatin architectureMultiplexed imagingChromatin loopsChromatin foldingGenomic functionsNuclear laminaGenomic regionsRNA speciesMultiple genomesGene expressionCopy numberCell typesDe novoGenomeSame cellsLamina-Dependent Stretching and Unconventional Chromosome Compartments in Early C. elegans Embryos
Sawh AN, Shafer MER, Su JH, Zhuang X, Wang S, Mango SE. Lamina-Dependent Stretching and Unconventional Chromosome Compartments in Early C. elegans Embryos. Molecular Cell 2020, 78: 96-111.e6. PMID: 32105612, PMCID: PMC7263362, DOI: 10.1016/j.molcel.2020.02.006.Peer-Reviewed Original ResearchConceptsB compartmentsEmbryonic chromosomesChromosome compartmentsInactive compartmentsChromosome domainsNuclear laminaEntire autosomesChromosomesCompartment boundariesUnappreciated roleDiverse conformationsDevelopmental contextChromosome stretchingCompartmentsConformationAutosomesChromatinGastrulationEmbryogenesisVariable positioningLaminaEmbryos
2017
Super-Resolution Fluorescence Imaging of Spatial Organization of Proteins and Lipids in Natural Rubber
Wu J, Qu W, Huang G, Wang S, Huang C, Liu H. Super-Resolution Fluorescence Imaging of Spatial Organization of Proteins and Lipids in Natural Rubber. Biomacromolecules 2017, 18: 1705-1712. PMID: 28463484, DOI: 10.1021/acs.biomac.6b01827.Peer-Reviewed Original ResearchConceptsMechanical propertiesNatural rubberSuperior mechanical propertiesEffective cross-linking densityNR latex particlesLiquid-like behaviorCross-linking densityStructure-property relationshipsPolymeric materialsHigh elasticityRubberGreat potentialDeproteinized natural rubberPolyisoprene rubberLatex particlesPropertiesSynthetic counterpartsStorm measurementsNanocompositesLayerMorphology of proteinsAggregatesParticlesElasticitySurface
2016
Spatial organization of chromatin domains and compartments in single chromosomes
Wang S, Su JH, Beliveau BJ, Bintu B, Moffitt JR, Wu CT, Zhuang X. Spatial organization of chromatin domains and compartments in single chromosomes. Science 2016, 353: 598-602. PMID: 27445307, PMCID: PMC4991974, DOI: 10.1126/science.aaf8084.Peer-Reviewed Original ResearchConceptsIndividual chromosomesChromatin domainsX chromosomeNumerous genomic regionsSpatial organizationInactive X chromosomeGenome functionChromatin organizationGenomic regionsFractal globule modelSingle chromosomePolarized mannerChromosomesDifferent foldingTADCompartmentsAutosomesChromatinDomainTADsFoldingRegulationCapture studiesAn RNA-aptamer-based two-color CRISPR labeling system
Wang S, Su JH, Zhang F, Zhuang X. An RNA-aptamer-based two-color CRISPR labeling system. Scientific Reports 2016, 6: 26857. PMID: 27229896, PMCID: PMC4882555, DOI: 10.1038/srep26857.Peer-Reviewed Original ResearchConceptsSingle guide RNAsDifferent fluorescent proteinsGenomic lociFluorescent proteinSpecific chromatin lociEndogenous genomic lociDynamics of chromatinPP7 coat proteinTarget genomic lociStem loop 2Essential biological functionsSpecific DNA sequencesDifferent bacterial speciesChromatin imagingCRISPR single guide RNAsChromatin lociRepetitive sequencesDNA sequencesChromatin labelingCoat proteinBiological functionsHuman cellsLoop 2RNA aptamersBacterial speciesSpatial organization shapes the turnover of a bacterial transcriptome
Moffitt JR, Pandey S, Boettiger AN, Wang S, Zhuang X. Spatial organization shapes the turnover of a bacterial transcriptome. ELife 2016, 5: e13065. PMID: 27198188, PMCID: PMC4874777, DOI: 10.7554/elife.13065.Peer-Reviewed Original ResearchConceptsBacterial transcriptomesSpatial organizationE. coli transcriptomeCo-translational insertionInner membrane proteinProtein mRNASignal recognition particlePost-transcriptional fatePost-transcriptional regulationSuper-resolution microscopyRNA degradosomePeriplasmic proteinsSignal peptideRNA sequencingTranscriptomeMembrane enrichmentSelective destabilizationMRNARNAProteinDegradosomeEukaryotesMembraneProkaryotesPowerful meansSuper-resolution imaging reveals distinct chromatin folding for different epigenetic states
Boettiger AN, Bintu B, Moffitt JR, Wang S, Beliveau BJ, Fudenberg G, Imakaev M, Mirny LA, Wu CT, Zhuang X. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 2016, 529: 418-422. PMID: 26760202, PMCID: PMC4905822, DOI: 10.1038/nature16496.Peer-Reviewed Original Research
2015
Spatially resolved, highly multiplexed RNA profiling in single cells
Chen KH, Boettiger AN, Moffitt JR, Wang S, Zhuang X. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 2015, 348: aaa6090. PMID: 25858977, PMCID: PMC4662681, DOI: 10.1126/science.aaa6090.Peer-Reviewed Original ResearchConceptsRNA speciesMultiplexed error-robust fluorescenceSingle-molecule imaging approachesDistinct RNA speciesIndividual cellsGene regulatory networksPairs of genesSingle cellsDistinct spatial distribution patternsUnannotated genesSingle-molecule labelingRegulatory networksNovel functionRNA profilingExpression profilesCellular behaviorCopy numberSitu hybridizationRich repertoireSpatial distribution patternsGenesDistribution patternsSpeciesCellsSpatial landscape