Featured Publications
Enhanced FIB-SEM systems for large-volume 3D imaging
Xu CS, Hayworth KJ, Lu Z, Grob P, Hassan AM, García-Cerdán JG, Niyogi KK, Nogales E, Weinberg RJ, Hess HF. Enhanced FIB-SEM systems for large-volume 3D imaging. ELife 2017, 6: e25916. PMID: 28500755, PMCID: PMC5476429, DOI: 10.7554/elife.25916.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChlamydomonas reinhardtiiDrosophilaImaging, Three-DimensionalMice, Inbred C57BLMicroscopy, Electron, ScanningNeuronsConceptsFIB-SEM systemFocused Ion Beam Scanning Electron MicroscopyIon beam scanning electron microscopyBeam scanning electron microscopyLong-term system stabilityScanning electron microscopyNovel high-resolution techniqueSystem stabilityFIB-SEMElectron microscopyHigh resolutionHigh-resolution techniquesSmall volumeCorrelative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells
Hoffman DP, Shtengel G, Xu CS, Campbell KR, Freeman M, Wang L, Milkie DE, Pasolli HA, Iyer N, Bogovic JA, Stabley DR, Shirinifard A, Pang S, Peale D, Schaefer K, Pomp W, Chang CL, Lippincott-Schwartz J, Kirchhausen T, Solecki DJ, Betzig E, Hess HF. Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells. Science 2020, 367 PMID: 31949053, PMCID: PMC7339343, DOI: 10.1126/science.aaz5357.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCell Line, TumorCellsChlorocebus aethiopsCOS CellsCryoelectron MicroscopyFreezingHeLa CellsHumansImaging, Three-DimensionalMiceMicroscopy, FluorescenceConceptsCorrelative super-resolution fluorescenceEndoplasmic reticulum-associated proteinSuper-resolution fluorescenceChromatin domainsMammalian cellsBlock-face electron microscopyDistinct proteinsTranscriptional activityBiochemical needsSpatial compartmentalizationIntranuclear vesiclesUltrastructural variabilityFrozen cellsWhole cellsFluorescence retentionCultured neuronsProteinCellsElectron microscopyCompartmentalizationVesiclesUltrastructureAdhesionDomainFluorescenceThree-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch
Handler A, Zhang Q, Pang S, Nguyen T, Iskols M, Nolan-Tamariz M, Cattel S, Plumb R, Sanchez B, Ashjian K, Shotland A, Brown B, Kabeer M, Turecek J, DeLisle M, Rankin G, Xiang W, Pavarino E, Africawala N, Santiago C, Lee W, Xu C, Ginty D. Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch. Neuron 2023, 111: 3211-3229.e9. PMID: 37725982, PMCID: PMC10773061, DOI: 10.1016/j.neuron.2023.08.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsImaging, Three-DimensionalIon ChannelsMammalsMechanoreceptorsMechanotransduction, CellularMerkel CellsMotion of VAPB molecules reveals ER–mitochondria contact site subdomains
Obara C, Nixon-Abell J, Moore A, Riccio F, Hoffman D, Shtengel G, Xu C, Schaefer K, Pasolli H, Masson J, Hess H, Calderon C, Blackstone C, Lippincott-Schwartz J. Motion of VAPB molecules reveals ER–mitochondria contact site subdomains. Nature 2024, 626: 169-176. PMID: 38267577, PMCID: PMC10830423, DOI: 10.1038/s41586-023-06956-y.Peer-Reviewed Original ResearchConceptsContact sitesExchange of signaling moleculesInterorganelle communicationOrganelle tetheringEukaryotic cellsSingle-molecule imagingCellular physiologyThree-dimensional electron microscopyMembrane curvatureSignaling moleculesExchange of moleculesDynamic subdomainsNanoscale organizationProtein BMetabolic needsSubdomainsCellsSitesMutationsMoleculesRemodelingSites1,2HomeostasisCommunication hubRegulation3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cells
Müller A, Schmidt D, Xu CS, Pang S, D’Costa J, Kretschmar S, Münster C, Kurth T, Jug F, Weigert M, Hess HF, Solimena M. 3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cells. Journal Of Cell Biology 2020, 220: e202010039. PMID: 33326005, PMCID: PMC7748794, DOI: 10.1083/jcb.202010039.Peer-Reviewed Original ResearchConceptsInsulin secretory granulesΒ-cellsSecretory granulesPrimary mammalian cellsFirst 3D reconstructionPrimary mouse β-cellsMouse β-cellsMammalian cellsMicrotubule organizationPlasma membraneIntracellular traffickingIslet β-cellsMicrotubule networkMicrotubulesUnprecedented resolutionCell constituentsMicrotubule numberCell functionGolgi apparatiCentriolesCellsEndocrine cellsGlucose stimulationEndomembranesGranulesContacts between the endoplasmic reticulum and other membranes in neurons
Wu Y, Whiteus C, Xu CS, Hayworth KJ, Weinberg RJ, Hess HF, De Camilli P. Contacts between the endoplasmic reticulum and other membranes in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e4859-e4867. PMID: 28559323, PMCID: PMC5474793, DOI: 10.1073/pnas.1701078114.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER–plasma membrane contactsER-PM contactsMembrane contactSmaller focal contactsRegulation of CaInterorganelle communicationOrganelle biogenesisDifferent neuronal compartmentsCell physiologyIntracellular membranesFocal contactsMultivesicular bodiesER contactsIntracellular organellesER cisternaeLipid homeostasisBiochemical studiesTubulovesicular structuresMembrane appositionNeuronal compartmentsImportant functionsMitochondriaReticulumMembrane
2019
Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolution
Hayworth K, Peale D, Januszewski M, Knott G, Lu Z, Xu C, Hess H. Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolution. Nature Methods 2019, 17: 68-71. PMID: 31740820, DOI: 10.1038/s41592-019-0641-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCerebral CortexDrosophila melanogasterImage Processing, Computer-AssistedImaging, Three-DimensionalMaleMiceMice, Inbred C57BLMicroscopy, Electron, ScanningTissue FixationConceptsIon beam scanning electron microscopyBeam scanning electron microscopyScanning electron microscopyThree-dimensional electron microscopy techniquesElectron microscopy techniquesIon millingIsotropic resolutionMicroscopy techniquesElectron microscopyThick tissue sectionsResolutionLarge tissue samplesMicroscopyMillingSectionsCortical column and whole-brain imaging with molecular contrast and nanoscale resolution
Gao R, Asano SM, Upadhyayula S, Pisarev I, Milkie DE, Liu TL, Singh V, Graves A, Huynh GH, Zhao Y, Bogovic J, Colonell J, Ott CM, Zugates C, Tappan S, Rodriguez A, Mosaliganti KR, Sheu SH, Pasolli HA, Pang S, Xu CS, Megason SG, Hess H, Lippincott-Schwartz J, Hantman A, Rubin GM, Kirchhausen T, Saalfeld S, Aso Y, Boyden ES, Betzig E. Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science 2019, 363 PMID: 30655415, PMCID: PMC6481610, DOI: 10.1126/science.aau8302.Peer-Reviewed Original ResearchConceptsDopaminergic neuronsDendritic spinesMouse cortexPresynaptic densitySynaptic proteinsBrain regionsLarge-scale studiesCortical columnsLattice light-sheet microscopyNeural activityNeural developmentSpecific molecular constituentsBrainLight-sheet microscopyDegree of stereotypyNanoscale spatial relationshipExpansion microscopy
2015
Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics
Hayworth K, Xu C, Lu Z, Knott G, Fetter R, Tapia J, Lichtman J, Hess H. Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics. Nature Methods 2015, 12: 319-322. PMID: 25686390, PMCID: PMC4382383, DOI: 10.1038/nmeth.3292.Peer-Reviewed Original Research
2012
Correlative 3D superresolution fluorescence and electron microscopy reveal the relationship of mitochondrial nucleoids to membranes
Kopek BG, Shtengel G, Xu CS, Clayton DA, Hess HF. Correlative 3D superresolution fluorescence and electron microscopy reveal the relationship of mitochondrial nucleoids to membranes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 6136-6141. PMID: 22474357, PMCID: PMC3341004, DOI: 10.1073/pnas.1121558109.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsDNA, MitochondrialDNA-Binding ProteinsFibroblastsHigh Mobility Group ProteinsImaging, Three-DimensionalLuminescent ProteinsMiceMicroscopy, ElectronMicroscopy, FluorescenceMicroscopy, InterferenceMitochondriaMitochondrial MembranesMitochondrial ProteinsReproducibility of ResultsConceptsMitochondrial nucleoidsSuperresolution fluorescenceIon beam ablationOptical microscopy techniquesFluorescent protein labelsCellular contextUltrastructural contextDirect imagingBiological questionsBiological processesSpecific proteinsCellular ultrastructureSuperresolution microscopyProtein labelCellular architectureFluorescence microscopyLocalization microscopyEM imagesNucleoidsMicroscopy techniquesProteinSample preparation protocolElectron microscopyVivo natureMicroscopy