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 scanningMicroscopyMethods of enhanced FIB-SEM sample preparation and image acquisition
Pang S, Xu C. Methods of enhanced FIB-SEM sample preparation and image acquisition. Methods In Cell Biology 2023, 177: 269-300. PMID: 37451770, DOI: 10.1016/bs.mcb.2023.01.019.ChaptersTransforming FIB-SEM Systems for Large-Volume Connectomics and Cell Biology
Xu C, Pang S, Hayworth K, Hess H. Transforming FIB-SEM Systems for Large-Volume Connectomics and Cell 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 volumesWhole-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 ResearchA serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility
Sheu SH, Upadhyayula S, Dupuy V, Pang S, Deng F, Wan J, Walpita D, Pasolli HA, Houser J, Sanchez-Martinez S, Brauchi SE, Banala S, Freeman M, Xu CS, Kirchhausen T, Hess HF, Lavis L, Li Y, Chaumont-Dubel S, Clapham DE. A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility. Cell 2022, 185: 3390-3407.e18. PMID: 36055200, PMCID: PMC9789380, DOI: 10.1016/j.cell.2022.07.026.Peer-Reviewed Original ResearchConceptsCA1 pyramidal neuronsChromatin accessibilityPyramidal neuronsSerotonergic axonsEpigenetic statePrimary ciliaHippocampal CA1 pyramidal neuronsChemogenetic stimulationSerotonin receptorsNuclear actinReceptor 6Histone acetylationAxonsChemical synapsesIntercellular communicationRhoA pathwaySynapseNeuronsCiliaSynapsesStimulationPathwayNeurotransmissionReceptorsThree-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 ResearchSpatial 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 architectureRibosomeProtein1ReticulumRemodelingZonationInteractionStructure, 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 reconstructionInteraction3D 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 stimulationEndomembranesGranulesPeriodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites
Benedetti L, Fan R, Weigel A, Moore A, Houlihan P, Kittisopikul M, Park G, Petruncio A, Hubbard P, Pang S, Xu C, Hess H, Saalfeld S, Rangaraju V, Clapham D, De Camilli P, Ryan T, Lippincott-Schwartz J. Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites. Cell 2024, 188: 484-500.e22. PMID: 39708809, DOI: 10.1016/j.cell.2024.11.029.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum-plasma membrane junctionsEndoplasmic reticulum-plasma membranePlasma membrane of dendritesVoltage-gated Ca<sup>2+</sup> channelsER-plasma membrane junctionsMembrane of dendritesProtein kinase IIRyanodine receptorSynaptic inputsDendritic computationsSpine stimulationNeuronal dendritesKinase IIIntracellular signalingMembrane junctionsPlasma membraneER tubulesSignal propagationSignal transmissionSubcellular architectureRyanodineLadder-like arraysLocal activationReleaseDendritesCorrelative 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 microscopyCompartmentalizationVesiclesUltrastructureAdhesionDomainFluorescenceNeuron-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 microscopyCOPII 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 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
2024
The physical and cellular mechanism of structural color change in zebrafish
Gur D, Moore A, Deis R, Pang S, Wu X, Pinkas I, Deo C, Iyer N, Hess H, Hammer J, Lippincott-Schwartz J. The physical and cellular mechanism of structural color change in zebrafish. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2308531121. PMID: 38805288, PMCID: PMC11161791, DOI: 10.1073/pnas.2308531121.Peer-Reviewed Original ResearchConceptsMicrotubule organizing centerCellular machineryFluorescence light microscopyOrganizing centerPharmacological perturbationsDyneinIridophoresRegulate body temperatureMicrotubulesCellular mechanismsIntracellular cAMPZebrafishMachineryIntracellular crystalsIon beam scanning electron microscopyGuanine crystalsStructural color changeLight microscopyColor changePeriodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites
Lorena Benedetti, Ruolin Fan, Aubrey V. Weigel, Andrew S. Moore, Patrick R. Houlihan, Mark Kittisopikul, Grace Park, Alyson Petruncio, Philip M. Hubbard, Song Pang, C. Shan Xu, Harald F. Hess, Stephan Saalfeld, Vidhya Rangaraju, David E. Clapham, Pietro De Camilli, Timothy A. Ryan, Jennifer Lippincott-Schwartz bioRxiv 2024.05.27.596121; DOI: 10.1101/2024.05.27.596121Peer-Reviewed Original ResearchHigh 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