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 ResearchConceptsFIB-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 volumeAn 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 microscopyCompartmentalizationVesiclesUltrastructureAdhesionDomainFluorescenceA connectome and analysis of the adult Drosophila central brain
Scheffer LK, Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang GB, Shinomiya K, Maitlin-Shepard J, Berg S, Clements J, Hubbard PM, Katz WT, Umayam L, Zhao T, Ackerman D, Blakely T, Bogovic J, Dolafi T, Kainmueller D, Kawase T, Khairy KA, Leavitt L, Li PH, Lindsey L, Neubarth N, Olbris DJ, Otsuna H, Trautman ET, Ito M, Bates AS, Goldammer J, Wolff T, Svirskas R, Schlegel P, Neace E, Knecht CJ, Alvarado CX, Bailey DA, Ballinger S, Borycz JA, Canino BS, Cheatham N, Cook M, Dreher M, Duclos O, Eubanks B, Fairbanks K, Finley S, Forknall N, Francis A, Hopkins GP, Joyce EM, Kim S, Kirk NA, Kovalyak J, Lauchie S, Lohff A, Maldonado C, Manley EA, McLin S, Mooney C, Ndama M, Ogundeyi O, Okeoma N, Ordish C, Padilla N, Patrick CM, Paterson T, Phillips EE, Phillips EM, Rampally N, Ribeiro C, Robertson MK, Rymer JT, Ryan SM, Sammons M, Scott AK, Scott AL, Shinomiya A, Smith C, Smith K, Smith NL, Sobeski MA, Suleiman A, Swift J, Takemura S, Talebi I, Tarnogorska D, Tenshaw E, Tokhi T, Walsh JJ, Yang T, Horne JA, Li F, Parekh R, Rivlin PK, Jayaraman V, Costa M, Jefferis GS, Ito K, Saalfeld S, George R, Meinertzhagen I, Rubin GM, Hess HF, Jain V, Plaza SM. A connectome and analysis of the adult Drosophila central brain. ELife 2020, 9: e57443. PMID: 32880371, PMCID: PMC7546738, DOI: 10.7554/elife.57443.Peer-Reviewed Original ResearchConceptsCentral brainDrosophila central brainAdult Drosophila Central BrainGenetic reagentsFruit flyComputational compartmentsFly brainExhaustive atlasCell typesAnimal behaviorNeural motifsChemical synapsesDrosophilaSuch large data setsNeural circuitsFliesCompartmentalizationLarge fractionMotifSynapsesCell exampleCompartmentsNeuronsElectrical consequencesWhole-cell organelle segmentation in volume electron microscopy
Heinrich L, Bennett D, Ackerman D, Park W, Bogovic J, Eckstein N, Petruncio A, Clements J, Pang S, Xu CS, Funke J, Korff W, Hess HF, Lippincott-Schwartz J, Saalfeld S, Weigel AV. Whole-cell organelle segmentation in volume electron microscopy. Nature 2021, 599: 141-146. PMID: 34616042, DOI: 10.1038/s41586-021-03977-3.Peer-Reviewed Original ResearchConceptsAutomatic reconstructionDeep learning architectureLearning architectureWeb repositoriesOpen dataAutomatic methodThree-dimensional reconstructionSuch methodsVolume electron microscopyQueriesSegmentationRepositoryArchitectureComputer codeSpatial interactionsDatasetReconstructionImagesMetricsCodeSuch reconstructionsRegulation 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 ResearchThree-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 Research3D 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
2024
Spatial 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
2023
A complete reconstruction of the early visual system of an adult insect
Chua N, Makarova A, Gunn P, Villani S, Cohen B, Thasin M, Wu J, Shefter D, Pang S, Xu C, Hess H, Polilov A, Chklovskii D. A complete reconstruction of the early visual system of an adult insect. Current Biology 2023, 33: 4611-4623.e4. PMID: 37774707, DOI: 10.1016/j.cub.2023.09.021.Peer-Reviewed Original Research3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle
Nikolaev Y, Ziolkowski L, Pang S, Li W, Feketa V, Xu C, Gracheva E, Bagriantsev S. 3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle. Science Advances 2023, 9: eadi4147. PMID: 37703368, PMCID: PMC10499330, DOI: 10.1126/sciadv.adi4147.Peer-Reviewed Original ResearchMultiscale head anatomy of Megaphragma (Hymenoptera: Trichogrammatidae)
Desyatirkina I, Makarova A, Pang S, Xu C, Hess H, Polilov A. Multiscale head anatomy of Megaphragma (Hymenoptera: Trichogrammatidae). Arthropod Structure & Development 2023, 76: 101299. PMID: 37666087, DOI: 10.1016/j.asd.2023.101299.Peer-Reviewed Original ResearchConceptsThree-dimensional electron microscopyParasitoid waspsLarge insectsEvolutionary benefitsTracheal systemWhole insectsMorphological workSubcellular structuresSubcellular levelInsectsSpeciesStomatogastric nervous systemMegaphragmaNeuron nucleiNucleated cellsWaspsGenusSet of musclesNervous systemOrgan systemsMicroinsectsComplexity of organizationsStructural planUltrastructureCellsComparative connectomics and escape behavior in larvae of closely related Drosophila species
Zhu J, Boivin J, Pang S, Xu C, Lu Z, Saalfeld S, Hess H, Ohyama T. Comparative connectomics and escape behavior in larvae of closely related Drosophila species. Current Biology 2023, 33: 2491-2503.e4. PMID: 37285846, DOI: 10.1016/j.cub.2023.05.043.Peer-Reviewed Original ResearchConceptsRelated Drosophila speciesDrosophila speciesEscape behaviorDrosophilid speciesRelated speciesMelanogasterSantomeaVentral nerve cordPlausible mechanistic explanationCommon partnerBehavioral traitsMolecular componentsNoxious cuesComparative connectomicsUnderlying neural circuitsSpeciesDownstream partnersMDIVMechanistic explanation
2022
En bloc preparation of Drosophila brains enables high-throughput FIB-SEM connectomics
Lu Z, Xu C, Hayworth K, Pang S, Shinomiya K, Plaza S, Scheffer L, Rubin G, Hess H, Rivlin P, Meinertzhagen I. En bloc preparation of Drosophila brains enables high-throughput FIB-SEM connectomics. Frontiers In Neural Circuits 2022, 16: 917251. PMID: 36589862, PMCID: PMC9801301, DOI: 10.3389/fncir.2022.917251.Peer-Reviewed Original ResearchThe 3D ultrastructure of the chordotonal organs in the antenna of a microwasp remains complex although simplified
Diakova A, Makarova A, Pang S, Xu C, Hess H, Polilov A. The 3D ultrastructure of the chordotonal organs in the antenna of a microwasp remains complex although simplified. Scientific Reports 2022, 12: 20172. PMID: 36424494, PMCID: PMC9691716, DOI: 10.1038/s41598-022-24390-4.Peer-Reviewed Original ResearchTransverse 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