C. Shan Xu, PhD
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Research Summary
Our primary research interest is transformative instrumentation development. At the forefront of volume Electron Microscopy (vEM), we aim to develop next generation technologies to enable discoveries from engineering to life science to clinical applications.
Extensive Research Description
Focused ion beam scanning electron microscopy (FIB-SEM) is a technique that has been used in materials science and the semiconductor industry for many decades. It uses a fine focused ion beam (FIB) as a micro sculpting tool to shape the specimen, then images the newly exposed surface with a scanning electron beam. FIB-SEM has been applied to biological imaging since 2006. Biological tissues are typically stained with heavy metals, such as osmium, which binds preferentially to the cell membranes and lipids thus enhancing the electron scattering signal at such locations. After imaging, the focused ion beam, typically comprising 30 keV gallium ions, strafes across the imaged surface and ablates a few nanometers from the top of the sample to expose a new and slightly deeper surface for subsequent imaging. Cycles of milling and imaging gradually erode away the sample while enabling the collection of a stack of consecutive 2D images, usually requiring tens of seconds to a few minutes per cycle. Such a continuous milling/imaging process generates a stack of 3D data with fine isotropic resolution (< 10 nm in x, y, and z) and excellent registration, also avoids many of the defects, such as tears and folds associated with cutting thin sections required for transmission electron microscopy. However, the conventional FIB-SEM platform comes at the cost of slower imaging speeds and lack of long-term system stability, which in turn limits the acquisition volume.
To enable FIB-SEM for large volume high resolution imaging, we redesigned the system architecture and transformed FIB-SEM from a conventional system lacking long term reliability to a robust imaging platform with 100% effective reliability: capable of years of continuous imaging without defects in the final image stack (Xu et al., eLife 2017; US patent 10,600,615; Xu et al., Neuromethods 2020).
Larger Volume
This enhanced FIB-SEM technology (developed at Janelia) has expanded the maximum imageable volume by orders of magnitude, enabling numerous transformational discoveries in life science, many of which were major new landmarks in their fields. Particularly, the largest connectome to date has been generated (Xu et al., 2020), where the superior z resolution empowers automated tracing of neuronal processes and reduces the time-consuming human proofreading effort. The journey of enhanced FIB-SEM development and Drosophila hemibrain endeavor were featured in Nature & New York Times.
Higher Resolution
Higher resolution further improves the interpretation of otherwise ambiguous details. By trading off against imaging speed, nearly all organelles can be resolved and classified with whole cell imaging at 4 x 4 x 4 nm3 voxels. Additionally, by combining with super-resolution fluorescence imaging, the CLEM applicationsunleash the full potential of intracellular organelle identification with labeling insights. We have established an isotropic 3D reference library of whole cells and tissues (Xu et al., Nature 2021) at the finest isotropic resolution to date, with open access to all datasets in OpenOrganelle (Heinrich et al., Nature 2021). The story was featured in Nature and TheScientist.
Future Developments
We aim to create new technology platforms beyond enhanced FIB-SEM to enable finer resolution and artifact-free isotropic high-resolution 3D imaging.
Despite how much the enhanced FIB-SEM technology has contributed, the 4-nm isotropic resolution falls short of robust visualization of 3D ultrastructure of sub-10 nm features. My lab aims to transcend the SEM resolution limit to date. Such a technology does not currently exist. With success, it will bridge the fields that are currently not connected: structural biology and cell biology, in the context of probing architecture across scales from protein to organelle to cell, within its native tissue environments.
In addition, we contemplate a 3D cryo-FIB-SEM technology that can reliably image a block of vitreously frozen cells or tissues with good contrast and without the need of heavy metal staining, dehydration, and plastic embedding. This streamlined approach will offer the potential to bypass tedious EM sample preparation needed to be individually optimized for large variety of tissues from different species. Most importantly, it allows the volume EM to unveil the fine details of cells and tissues in their native states.
Coauthors
Research Interests
Biophysics; Engineering; Microscopy, Electron; Neurosciences; Physiology
Selected Publications
- A complete reconstruction of the early visual system of an adult insectChua 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 PMID: 37774707, DOI: 10.1016/j.cub.2023.09.021.
- 3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscleNikolaev 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.
- Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touchHandler 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 PMID: 37725982, DOI: 10.1016/j.neuron.2023.08.023.
- Multiscale 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.
- Comparative connectomics and escape behavior in larvae of closely related Drosophila speciesZhu 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.
- Methods of enhanced FIB-SEM sample preparation and image acquisitionPang S, Xu C. Methods of enhanced FIB-SEM sample preparation and image acquisition. 2023, 177: 269-300. PMID: 37451770, DOI: 10.1016/bs.mcb.2023.01.019.
- Methods of enhanced FIB-SEM sample preparation and image acquisitionPang S, Xu C. Methods of enhanced FIB-SEM sample preparation and image acquisition. 2023 DOI: 10.1016/bs.mcb.2023.01.019.
- En bloc preparation of Drosophila brains enables high-throughput FIB-SEM connectomicsLu 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.
- The 3D ultrastructure of the chordotonal organs in the antenna of a microwasp remains complex although simplifiedDiakova 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.
- A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibilitySheu 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.
- ESCRT-mediated membrane repair protects tumor-derived cells against T cell attackRitter 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.
- 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.
- Regulation of liver subcellular architecture controls metabolic homeostasisParlakgül 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.
- An open-access volume electron microscopy atlas of whole cells and tissuesXu 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.
- Whole-cell organelle segmentation in volume electron microscopyHeinrich 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.
- ER-to-Golgi protein delivery through an interwoven, tubular network extending from ERWeigel 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.
- Protocol for preparation of heterogeneous biological samples for 3D electron microscopy: a case study for insects.Polilov AA, Makarova AA, Pang S, Shan Xu C, Hess H. Protocol for preparation of heterogeneous biological samples for 3D electron microscopy: a case study for insects. Scientific Reports 2021, 11: 4717. PMID: 33633143, PMCID: PMC7907262, DOI: 10.1038/s41598-021-83936-0.
- 3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cellsMüller 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.
- Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesinMiron E, Oldenkamp R, Brown JM, Pinto DMS, Xu CS, Faria AR, Shaban HA, Rhodes JDP, Innocent C, de Ornellas S, Hess HF, Buckle V, Schermelleh L. Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin. Science Advances 2020, 6: eaba8811. PMID: 32967822, PMCID: PMC7531892, DOI: 10.1126/sciadv.aba8811.
- A connectome and analysis of the adult Drosophila central brainScheffer 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.
- Transforming FIB-SEMFocused Ion Beam Scanning Electron Microscopy (FIB-SEM) Systems for Large-Volume ConnectomicsConnectomics and Cell BiologyCell biologyXu 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. 2020, 155: 221-243. DOI: 10.1007/978-1-0716-0691-9_12.
- Chloroplast Sec14-like 1 (CPSFL1) is essential for normal chloroplast development and affects carotenoid accumulation in ChlamydomonasGarcÃa-Cerdán JG, Schmid EM, Takeuchi T, McRae I, McDonald KL, Yordduangjun N, Hassan AM, Grob P, Xu CS, Hess HF, Fletcher DA, Nogales E, Niyogi KK. Chloroplast Sec14-like 1 (CPSFL1) is essential for normal chloroplast development and affects carotenoid accumulation in Chlamydomonas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 12452-12463. PMID: 32404426, PMCID: PMC7275715, DOI: 10.1073/pnas.1916948117.
- Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cellsHoffman 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.
- Transforming FIB-SEM Systems for Large-Volume Connectomics and Cell BiologyXu, C.S., Pang, S., Hayworth, K.J., Hess, H.F. (2020). Transforming FIB-SEM Systems for Large-Volume Connectomics and Cell Biology. In: Wacker, I., Hummel, E., Burgold, S., Schröder, R. (eds) Volume Microscopy . Neuromethods, vol 155. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0691-9_12
- Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolutionHayworth 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.
- Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-IIIChang 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.
- Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid ToxicityIoannou 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.
- Cortical column and whole-brain imaging with molecular contrast and nanoscale resolutionGao 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.
- Comparisons between the ON- and OFF-edge motion pathways in the Drosophila brainShinomiya K, Huang G, Lu Z, Parag T, Xu CS, Aniceto R, Ansari N, Cheatham N, Lauchie S, Neace E, Ogundeyi O, Ordish C, Peel D, Shinomiya A, Smith C, Takemura S, Talebi I, Rivlin PK, Nern A, Scheffer LK, Plaza SM, Meinertzhagen IA. Comparisons between the ON- and OFF-edge motion pathways in the Drosophila brain. ELife 2019, 8: e40025. PMID: 30624205, PMCID: PMC6338461, DOI: 10.7554/elife.40025.
- A resource for the Drosophila antennal lobe provided by the connectome of glomerulus VA1vHorne JA, Langille C, McLin S, Wiederman M, Lu Z, Xu CS, Plaza SM, Scheffer LK, Hess HF, Meinertzhagen IA. A resource for the Drosophila antennal lobe provided by the connectome of glomerulus VA1v. ELife 2018, 7: e37550. PMID: 30382940, PMCID: PMC6234030, DOI: 10.7554/elife.37550.
- The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular VesiclesCoulter 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.
- A connectome of a learning and memory center in the adult Drosophila brainTakemura SY, Aso Y, Hige T, Wong A, Lu Z, Xu CS, Rivlin PK, Hess H, Zhao T, Parag T, Berg S, Huang G, Katz W, Olbris DJ, Plaza S, Umayam L, Aniceto R, Chang LA, Lauchie S, Ogundeyi O, Ordish C, Shinomiya A, Sigmund C, Takemura S, Tran J, Turner GC, Rubin GM, Scheffer LK. A connectome of a learning and memory center in the adult Drosophila brain. ELife 2017, 6: e26975. PMID: 28718765, PMCID: PMC5550281, DOI: 10.7554/elife.26975.
- Contacts between the endoplasmic reticulum and other membranes in neuronsWu 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.
- Enhanced FIB-SEM systems for large-volume 3D imagingXu CS, Hayworth KJ, Lu Z, Grob P, Hassan AM, GarcÃa-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.
- Diverse protocols for correlative super-resolution fluorescence imaging and electron microscopy of chemically fixed samplesKopek BG, Paez-Segala MG, Shtengel G, Sochacki KA, Sun MG, Wang Y, Xu CS, van Engelenburg SB, Taraska JW, Looger LL, Hess HF. Diverse protocols for correlative super-resolution fluorescence imaging and electron microscopy of chemically fixed samples. Nature Protocols 2017, 12: 916-946. PMID: 28384138, PMCID: PMC5514615, DOI: 10.1038/nprot.2017.017.
- Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ERNixon-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.
- Synaptic circuits and their variations within different columns in the visual system of DrosophilaTakemura SY, Xu CS, Lu Z, Rivlin PK, Parag T, Olbris DJ, Plaza S, Zhao T, Katz WT, Umayam L, Weaver C, Hess HF, Horne JA, Nunez-Iglesias J, Aniceto R, Chang LA, Lauchie S, Nasca A, Ogundeyi O, Sigmund C, Takemura S, Tran J, Langille C, Le Lacheur K, McLin S, Shinomiya A, Chklovskii DB, Meinertzhagen IA, Scheffer LK. Synaptic circuits and their variations within different columns in the visual system of Drosophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 13711-13716. PMID: 26483464, PMCID: PMC4640747, DOI: 10.1073/pnas.1509820112.
- Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomicsHayworth K, Xu C, Lu Z, Knott G, Fetter R, Tapia J, Lichtman J, Hess H. Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics. Nature Methods 2015, 12: 319-322. PMID: 25686390, PMCID: PMC4382383, DOI: 10.1038/nmeth.3292.
- Correlative 3D superresolution fluorescence and electron microscopy reveal the relationship of mitochondrial nucleoids to membranesKopek 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.