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 microscopyCompartmentalizationVesiclesUltrastructureAdhesionDomainFluorescenceWhole-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 viewsTraffickingMicrotubulesProteinVesiclesPathwayCompartmentsMotion 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 hubRegulation
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
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
Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
Chang C, Weigel A, Ioannou M, Pasolli H, Xu C, Peale D, Shtengel G, Freeman M, Hess H, Blackstone C, Lippincott-Schwartz J. Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III. Journal Of Cell Biology 2019, 218: 2583-2599. PMID: 31227594, PMCID: PMC6683741, DOI: 10.1083/jcb.201902061.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid MotifsATP Binding Cassette Transporter, Subfamily D, Member 1Biological TransportEndosomal Sorting Complexes Required for TransportFatty AcidsHeLa CellsHumansHydrolysisLauric AcidsLipid DropletsModels, BiologicalMutant ProteinsOncogene ProteinsPeroxisomesSpastinConceptsFA traffickingLipid dropletsESCRT-III componentsNeutral lipid storage organellesLipid storage organellesFatty acid traffickingAAA-ATPaseESCRT-IIIDual roleMIT domainFatty acidsStorage organellesContact sitesPathogenesis of diseaseFA metabolismTraffickingPeroxisomesSpastinIST1OrganellesCHMP1BInterrelated mechanismsLipid peroxidationContact formationATPaseCortical 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
2016
Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER
Nixon-Abell J, Obara CJ, Weigel AV, Li D, Legant WR, Xu CS, Pasolli HA, Harvey K, Hess HF, Betzig E, Blackstone C, Lippincott-Schwartz J. Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER. Science 2016, 354: aaf3928-aaf3928. PMID: 27789813, PMCID: PMC6528812, DOI: 10.1126/science.aaf3928.Peer-Reviewed Original Research