Featured Publications
An open-access volume electron microscopy atlas of whole cells and tissues
Xu CS, Pang S, Shtengel G, Müller A, Ritter AT, Hoffman HK, Takemura SY, Lu Z, Pasolli HA, Iyer N, Chung J, Bennett D, Weigel AV, Freeman M, van Engelenburg SB, Walther TC, Farese RV, Lippincott-Schwartz J, Mellman I, Solimena M, Hess HF. An open-access volume electron microscopy atlas of whole cells and tissues. Nature 2021, 599: 147-151. PMID: 34616045, PMCID: PMC9004664, DOI: 10.1038/s41586-021-03992-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDatasets as TopicDrosophila melanogasterFemaleGolgi ApparatusHumansInformation DisseminationInterphaseIslets of LangerhansMaleMiceMicroscopy, Electron, ScanningMicrotubulesNeurogliaNeuronsOpen Access PublishingOrganellesOvarian NeoplasmsRibosomesSynaptic VesiclesT-Lymphocytes, CytotoxicConceptsDrosophila neural tissueWhole cellsThin-section electron microscopyVolume electron microscopyCellular architectureMouse pancreatic isletsCancer cellsEM tomographyCellular structureCellsCellular samplesNeural tissuePancreatic isletsEnhanced signal detectionAtlasBeam-scanning electron microscopyTissueElectron microscopyOpen access dataBiologyImmune cellsSubsequent analysisSEM scanningMicroscopyCorrelative 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 ResearchConceptsCorrelative super-resolution fluorescenceEndoplasmic reticulum-associated proteinSuper-resolution fluorescenceChromatin domainsMammalian cellsBlock-face electron microscopyDistinct proteinsTranscriptional activityBiochemical needsSpatial compartmentalizationIntranuclear vesiclesUltrastructural variabilityFrozen cellsWhole cellsFluorescence retentionCultured neuronsProteinCellsElectron microscopyCompartmentalizationVesiclesUltrastructureAdhesionDomainFluorescenceRegulation of liver subcellular architecture controls metabolic homeostasis
Parlakgül G, Arruda AP, Pang S, Cagampan E, Min N, Güney E, Lee GY, Inouye K, Hess HF, Xu CS, Hotamışlıgil GS. Regulation of liver subcellular architecture controls metabolic homeostasis. Nature 2022, 603: 736-742. PMID: 35264794, PMCID: PMC9014868, DOI: 10.1038/s41586-022-04488-5.Peer-Reviewed Original ResearchContacts 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
2024
Structure, interaction and nervous connectivity of beta cell primary cilia
Müller A, Klena N, Pang S, Garcia L, Topcheva O, Aurrecoechea Duran S, Sulaymankhil D, Seliskar M, Mziaut H, Schöniger E, Friedland D, Kipke N, Kretschmar S, Münster C, Weitz J, Distler M, Kurth T, Schmidt D, Hess H, Xu C, Pigino G, Solimena M. Structure, interaction and nervous connectivity of beta cell primary cilia. Nature Communications 2024, 15: 9168. PMID: 39448638, PMCID: PMC11502866, DOI: 10.1038/s41467-024-53348-5.Peer-Reviewed Original ResearchConceptsPrimary ciliaCell's primary ciliumNon-islet cellsPancreatic beta cellsCiliary pocketSensory organellesAxonemal organizationMotility componentsExtrinsic signalsStructural basisBeta cellsCiliaCell typesExpansion microscopyParacrine signalingIslet innervationCellsIsletsBetaAxonemeOrganellesSignalThree-dimensional reconstructionInteractionSpatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity
Parlakgül G, Pang S, Artico L, Min N, Cagampan E, Villa R, Goncalves R, Lee G, Xu C, Hotamışlıgil G, Arruda A. Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity. Nature Communications 2024, 15: 3982. PMID: 38729945, PMCID: PMC11087507, DOI: 10.1038/s41467-024-48272-7.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER-mitochondria interactionsSubcellular spatial organizationER-mitochondriaER sheetsNutritional fluctuationsFatty acid oxidationNutrient availabilityHepatic fatty acid oxidationMetabolic flexibilityVolume electron microscopyHepatic ERMitochondriaLiver zonationSpatial organizationAcid oxidationPericentral hepatocytesHepatocytesMolecular architectureRibosomeProtein1ReticulumRemodelingZonationInteraction
2022
Transverse endoplasmic reticulum expansion in hereditary spastic paraplegia corticospinal axons
Zhu PP, Hung HF, Batchenkova N, Nixon-Abell J, Henderson J, Zheng P, Renvoisé B, Pang S, Xu CS, Saalfeld S, Funke J, Xie Y, Svara F, Hess HF, Blackstone C. Transverse endoplasmic reticulum expansion in hereditary spastic paraplegia corticospinal axons. Human Molecular Genetics 2022, 31: 2779-2795. PMID: 35348668, PMCID: PMC9402237, DOI: 10.1093/hmg/ddac072.Peer-Reviewed Original Research
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 ResearchConceptsIon beam scanning electron microscopyBeam scanning electron microscopyScanning electron microscopyThree-dimensional electron microscopy techniquesElectron microscopy techniquesIon millingIsotropic resolutionMicroscopy techniquesElectron microscopyThick tissue sectionsResolutionLarge tissue samplesMicroscopyMillingSectionsNeuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z. Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity. Cell 2019, 177: 1522-1535.e14. PMID: 31130380, DOI: 10.1016/j.cell.2019.04.001.Peer-Reviewed Original ResearchConceptsGene expression programsLipid dropletsFatty acidsToxic fatty acidsMitochondrial β-oxidationNeuron-astrocyte couplingExpression programsMetabolic coordinationFatty acid toxicityFA toxicityCoordinated mechanismFA metabolismΒ-oxidationLipid metabolismHyperactive neuronsAcid toxicityNeuronal activityDisease statesNeuronsMetabolismNeural activityLipid particlesAstrocytesBrainHomeostasisCortical 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
2018
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Reports 2018, 24: 973-986.e8. PMID: 30044992, PMCID: PMC6178983, DOI: 10.1016/j.celrep.2018.06.100.Peer-Reviewed Original ResearchConceptsExtracellular vesiclesMultivesicular bodiesIntraluminal vesicle formationESCRT proteinsHedgehog secretionProgenitor maintenanceMolecular mechanistic insightsComplex proteinsCell communicationEV subtypesVesicle formationChmp1AAutosomal recessive microcephalyHuman cerebral organoidsSonic hedgehogProgenitor proliferationFunction mutationsImpairs secretionAdult functionMechanistic insightsCerebral organoidsNull micePontocerebellar hypoplasiaShhProtein
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