IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47066-1.html
   My bibliography  Save this article

Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling

Author

Listed:
  • Benjamin C. Creekmore

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Kathryn Kixmoeller

    (University of Pennsylvania
    University of Pennsylvania)

  • Ben E. Black

    (University of Pennsylvania
    University of Pennsylvania)

  • Edward B. Lee

    (University of Pennsylvania)

  • Yi-Wei Chang

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Ultrastructure of human brain tissue has traditionally been examined using electron microscopy (EM) following fixation, staining, and sectioning, which limit resolution and introduce artifacts. Alternatively, cryo-electron tomography (cryo-ET) allows higher resolution imaging of unfixed cellular samples while preserving architecture, but it requires samples to be vitreous and thin enough for transmission EM. Due to these requirements, cryo-ET has yet to be employed to investigate unfixed, never previously frozen human brain tissue. Here we present a method for generating lamellae in human brain tissue obtained at time of autopsy that can be imaged via cryo-ET. We vitrify the tissue via plunge-freezing and use xenon plasma focused ion beam (FIB) milling to generate lamellae directly on-grid at variable depth inside the tissue. Lamellae generated in Alzheimer’s disease brain tissue reveal intact subcellular structures including components of autophagy and potential pathologic tau fibrils. Furthermore, we reveal intact compact myelin and functional cytoplasmic expansions. These images indicate that plasma FIB milling with cryo-ET may be used to elucidate nanoscale structures within the human brain.

Suggested Citation

  • Benjamin C. Creekmore & Kathryn Kixmoeller & Ben E. Black & Edward B. Lee & Yi-Wei Chang, 2024. "Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47066-1
    DOI: 10.1038/s41467-024-47066-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47066-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47066-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Zvonimir Vrselja & Stefano G. Daniele & John Silbereis & Francesca Talpo & Yury M. Morozov & André M. M. Sousa & Brian S. Tanaka & Mario Skarica & Mihovil Pletikos & Navjot Kaur & Zhen W. Zhuang & Zha, 2019. "Restoration of brain circulation and cellular functions hours post-mortem," Nature, Nature, vol. 568(7752), pages 336-343, April.
    2. Martin Meschkat & Anna M. Steyer & Marie-Theres Weil & Kathrin Kusch & Olaf Jahn & Lars Piepkorn & Paola Agüi-Gonzalez & Nhu Thi Ngoc Phan & Torben Ruhwedel & Boguslawa Sadowski & Silvio O. Rizzoli & , 2022. "White matter integrity in mice requires continuous myelin synthesis at the inner tongue," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Yang Shi & Wenjuan Zhang & Yang Yang & Alexey G. Murzin & Benjamin Falcon & Abhay Kotecha & Mike Beers & Airi Tarutani & Fuyuki Kametani & Holly J. Garringer & Ruben Vidal & Grace I. Hallinan & Tammar, 2021. "Structure-based classification of tauopathies," Nature, Nature, vol. 598(7880), pages 359-363, October.
    4. Tristan Bepler & Kotaro Kelley & Alex J. Noble & Bonnie Berger, 2020. "Topaz-Denoise: general deep denoising models for cryoEM and cryoET," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    5. Casper Berger & Maud Dumoux & Thomas Glen & Neville B.-y. Yee & John M. Mitchels & Zuzana Patáková & Michele C. Darrow & James H. Naismith & Michael Grange, 2023. "Plasma FIB milling for the determination of structures in situ," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yun-Tao Liu & Heng Zhang & Hui Wang & Chang-Lu Tao & Guo-Qiang Bi & Z. Hong Zhou, 2022. "Isotropic reconstruction for electron tomography with deep learning," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Xinyu Zhang & Tianfang Zhao & Jiansheng Chen & Yuan Shen & Xueming Li, 2022. "EPicker is an exemplar-based continual learning approach for knowledge accumulation in cryoEM particle picking," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Mable Lam & Koji Takeo & Rafael G. Almeida & Madeline H. Cooper & Kathryn Wu & Manasi Iyer & Husniye Kantarci & J. Bradley Zuchero, 2022. "CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Erumbi S. Rangarajan & Julian L. Bois & Scott B. Hansen & Tina Izard, 2024. "High-resolution snapshots of the talin auto-inhibitory states suggest roles in cell adhesion and signaling," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Tim Schulte & Antonio Chaves-Sanjuan & Valentina Speranzini & Kevin Sicking & Melissa Milazzo & Giulia Mazzini & Paola Rognoni & Serena Caminito & Paolo Milani & Chiara Marabelli & Alessandro Corbelli, 2024. "Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Itika Saha & Patricia Yuste-Checa & Miguel Silva Padilha & Qiang Guo & Roman Körner & Hauke Holthusen & Victoria A. Trinkaus & Irina Dudanova & Rubén Fernández-Busnadiego & Wolfgang Baumeister & David, 2023. "The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Sambhasan Banerjee & Julian Baur & Christoph Daniel & Peter Benedikt Pfeiffer & Manuel Hitzenberger & Lukas Kuhn & Sebastian Wiese & Johan Bijzet & Christian Haupt & Kerstin U. Amann & Martin Zacharia, 2022. "Amyloid fibril structure from the vascular variant of systemic AA amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    8. Simon Wiedemann & Reinhard Heckel, 2024. "A deep learning method for simultaneous denoising and missing wedge reconstruction in cryogenic electron tomography," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Qiansheng Liang & Gamma Chi & Leonardo Cirqueira & Lianteng Zhi & Agostino Marasco & Nadia Pilati & Martin J. Gunthorpe & Giuseppe Alvaro & Charles H. Large & David B. Sauer & Werner Treptow & Manuel , 2024. "The binding and mechanism of a positive allosteric modulator of Kv3 channels," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Nicolai Franzmeier & Matthias Brendel & Leonie Beyer & Luna Slemann & Gabor G. Kovacs & Thomas Arzberger & Carolin Kurz & Gesine Respondek & Milica J. Lukic & Davina Biel & Anna Rubinski & Lukas Front, 2022. "Tau deposition patterns are associated with functional connectivity in primary tauopathies," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Luca Pinzi & Christian Conze & Nicolo Bisi & Gabriele Dalla Torre & Ahmed Soliman & Nanci Monteiro-Abreu & Nataliya I. Trushina & Andrea Krusenbaum & Maryam Khodaei Dolouei & Andrea Hellwig & Michael , 2024. "Quantitative live cell imaging of a tauopathy model enables the identification of a polypharmacological drug candidate that restores physiological microtubule interaction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Galina Limorenko & Meltem Tatli & Rajasekhar Kolla & Sergey Nazarov & Marie-Theres Weil & David C. Schöndorf & Daniela Geist & Peter Reinhardt & Dagmar E. Ehrnhoefer & Henning Stahlberg & Laura Gaspar, 2023. "Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Zhen Hou & Frank Nightingale & Yanan Zhu & Craig MacGregor-Chatwin & Peijun Zhang, 2023. "Structure of native chromatin fibres revealed by Cryo-ET in situ," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    14. Szymon W. Manka & Wenjuan Zhang & Adam Wenborn & Jemma Betts & Susan Joiner & Helen R. Saibil & John Collinge & Jonathan D. F. Wadsworth, 2022. "2.7 Å cryo-EM structure of ex vivo RML prion fibrils," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    15. Vishruth Mullapudi & Jaime Vaquer-Alicea & Vaibhav Bommareddy & Anthony R. Vega & Bryan D. Ryder & Charles L. White & Marc. I. Diamond & Lukasz A. Joachimiak, 2023. "Network of hotspot interactions cluster tau amyloid folds," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    16. Jianping Wu & Georg Kislinger & Jerome Duschek & Ayşe Damla Durmaz & Benedikt Wefers & Ruoqing Feng & Karsten Nalbach & Wolfgang Wurst & Christian Behrends & Martina Schifferer & Mikael Simons, 2024. "Nonvesicular lipid transfer drives myelin growth in the central nervous system," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. Luka Bacic & Guillaume Gaullier & Jugal Mohapatra & Guanzhong Mao & Klaus Brackmann & Mikhail Panfilov & Glen Liszczak & Anton Sabantsev & Sebastian Deindl, 2024. "Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    18. Yaejin Yun & Hyeongseop Jeong & Thibaut Laboute & Kirill A. Martemyanov & Hyung Ho Lee, 2024. "Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    19. Tomáš Kovaľ & Nabajyoti Borah & Petra Sudzinová & Barbora Brezovská & Hana Šanderová & Viola Vaňková Hausnerová & Alena Křenková & Martin Hubálek & Mária Trundová & Kristýna Adámková & Jarmila Dušková, 2024. "Mycobacterial HelD connects RNA polymerase recycling with transcription initiation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    20. Jianping Li & Yan Li & Akiko Koide & Huihui Kuang & Victor J. Torres & Shohei Koide & Da-Neng Wang & Nathaniel J. Traaseth, 2024. "Proton-coupled transport mechanism of the efflux pump NorA," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47066-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.