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 reconstructionsER-to-Golgi protein delivery through an interwoven, tubular network extending from ER
Weigel AV, Chang CL, Shtengel G, Xu CS, Hoffman DP, Freeman M, Iyer N, Aaron J, Khuon S, Bogovic J, Qiu W, Hess HF, Lippincott-Schwartz J. ER-to-Golgi protein delivery through an interwoven, tubular network extending from ER. Cell 2021, 184: 2412-2429.e16. PMID: 33852913, DOI: 10.1016/j.cell.2021.03.035.Peer-Reviewed Original ResearchConceptsTubular networkEarly secretory compartmentsAccurate traffickingProtein exportDiverse proteinsProtein localizationSecretory pathwayMammalian cellsSecretory compartmentsCargo entryGolgi apparatusLipid bilayersIllumination microscopyBeam scanning electron microscopyIon beam scanning electron microscopyProtein deliveryCOPIIERDynamic 3D viewsTraffickingMicrotubulesProteinVesiclesPathwayCompartmentsRegulation 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 ResearchESCRT-mediated membrane repair protects tumor-derived cells against T cell attack
Ritter AT, Shtengel G, Xu CS, Weigel A, Hoffman DP, Freeman M, Iyer N, Alivodej N, Ackerman D, Voskoboinik I, Trapani J, Hess HF, Mellman I. ESCRT-mediated membrane repair protects tumor-derived cells against T cell attack. Science 2022, 376: 377-382. PMID: 35446649, DOI: 10.1126/science.abl3855.Peer-Reviewed Original ResearchConceptsESCRT machineryEndosomal Sorting ComplexCancer-derived cellsESCRT proteinsTarget cellsTumor-derived cellsPlasma membranePerforin poresTransport proteinsMembrane woundsMembrane repairRelease of perforinMachineryCytosolProteinCellsCytolytic attackCytotoxic T lymphocytesESCRTTumor cellsPerforin releaseGranzymesRepairApoptosisCell attackThree-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 ResearchMotion 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 hubRegulationCOPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites
Liao Y, Pang S, Li W, Shtengel G, Choi H, Schaefer K, Xu C, Lippincott-Schwartz J. COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites. Developmental Cell 2024, 59: 1410-1424.e4. PMID: 38593803, DOI: 10.1016/j.devcel.2024.03.027.Peer-Reviewed Original ResearchEndoplasmic reticulum exit sitesER exit sitesAmino acid starvationPurified recombinant componentsExit siteProtein sortingSecretory pathwayMammalian cellsNutrient stressCellular conditionsEndoplasmic reticulumGiant unilamellar vesiclesTubular outgrowthsESCRTMicroautophagyNutrient stressorsALG2COPIILysosomesPathwayMTOR inhibitionUnilamellar vesiclesRecombinant componentsFocused ion beam scanning electron microscopyIon beam scanning electron microscopy3D 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 stimulationEndomembranesGranulesTransforming FIB-SEMFocused Ion Beam Scanning Electron Microscopy (FIB-SEM) Systems for Large-Volume ConnectomicsConnectomics and Cell BiologyCell biology
Xu C, Pang S, Hayworth K, Hess H. Transforming FIB-SEMFocused Ion Beam Scanning Electron Microscopy (FIB-SEM) Systems for Large-Volume ConnectomicsConnectomics and Cell BiologyCell biology. Neuromethods 2020, 155: 221-243. DOI: 10.1007/978-1-0716-0691-9_12.Peer-Reviewed Original ResearchScanning electron microscopy systemIon beam scanning electron microscopyBeam scanning electron microscopyElectron microscopy systemScanning electron microscopyElectron microscopyLong-term reliabilityScanning electron microscopy technologyRobust imaging platformElectron microscopy technologyConventional FIBMicroscopy systemHigh resolutionFIB-SEMResolution requirementsCell biology researchBoundary conditionsFinal image stackFIBMicroscopy technologyHigh-resolution imagingOrders of magnitudeImaging platformLarge sample volumesImage volumesContacts 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 architectureRibosomeProtein1ReticulumRemodelingZonationInteractionHigh Resolution Reconstruction of the Proximal Tubule Apical Endocytic Pathway
Lackner E, Pandya R, Burdyniuk M, Xu C, Pang S, Caplan M, Weisz O. High Resolution Reconstruction of the Proximal Tubule Apical Endocytic Pathway. Physiology 2024, 39: 998. DOI: 10.1152/physiol.2024.39.s1.998.Peer-Reviewed Original ResearchApical early endosomesDense apical tubulesApical endocytic pathwayEndocytic pathwayApical membraneMembrane invaginationsReceptor recyclingApical vacuolesInterconnected network of tubulesProximal tubulesPT cellsBase of microvilliNetwork of tubulesMultiligand receptor megalinEarly endosomesBudding vesiclesKidney proximal tubulesEndocytic compartmentsEndocytic entryEndosomal compartmentsApical tubulesStable compartmentsSubapical regionGlomerular filtration barrierApical uptakeVolume microscopic analysis of membrane contact sites in mouse kidney renal proximal tubule epithelial cells
Pandya R, Pang S, Lackner E, Reyna-Neyra A, Li W, Sy K, Burdyniuk M, Weisz O, Xu C, Caplan M. Volume microscopic analysis of membrane contact sites in mouse kidney renal proximal tubule epithelial cells. Physiology 2024, 39: 1086. DOI: 10.1152/physiol.2024.39.s1.1086.Peer-Reviewed Original ResearchMembrane contact sitesProximal tubule epithelial cellsTubule epithelial cellsEndoplasmic reticulumEpithelial cellsContact sitesPlasma membraneER volumeRenal proximal tubule epithelial cellsFunction of membrane contact sitesVolume of endoplasmic reticulumProximal tubule cellsInter-organelle communicationBasal-lateral surfacesRenal epithelial cellsAdvanced imaging techniquesMedian volumeTubule cellsMale miceCell plasma membraneRenal cortexScanning electron microscopyFIB-SEMMouse kidneySmooth ER
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 Research