Evidence map›Paper›PMID 31949053›Full record

ArticleScience (New York, N.Y.)2020

Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells.

David P Hoffman, Gleb Shtengel, C Shan Xu, Kirby R Campbell, Melanie Freeman, Lei Wang, Daniel E Milkie, H Amalia Pasolli, Nirmala Iyer, John A Bogovic and 12 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

171 citing papers in PubMed.

  1. Article
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  10. Article
  11. Article
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  14. Review
  15. Cryogenic light microscopy of vitrified samples with angstrom precision.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. Single-Molecule 3D Nanoscopy for Application to Cryofixed Samples.The journal of physical chemistry. B · 2025
    Article
  20. Time-deterministic cryo-optical microscopy.Light, science & applications · 2025
    Article

111 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

David P HoffmanJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0001-9327-0218
Gleb ShtengelJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0001-6830-640X
C Shan XuJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0002-8564-7836
Kirby R CampbellDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.ORCID 0000-0003-0091-4139
Melanie FreemanJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0002-3576-8664
Lei WangDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-0159-1987
Daniel E MilkieJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0002-3917-6965
H Amalia PasolliJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0003-3899-3530
Nirmala IyerJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0003-0202-4746
John A BogovicJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0002-4829-9457
Daniel R StableyNeuroimaging Laboratory, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abbas ShirinifardBioimage Analysis Core, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Song PangJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
David PealeJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0003-0756-4039
Kathy SchaeferJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0002-2898-8511
Wim PompDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-7623-2073
Chi-Lun ChangJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0003-0017-2243
Jennifer Lippincott-SchwartzJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0002-8601-3501
Tom KirchhausenJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.ORCID 0000-0003-0559-893X
David J SoleckiDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Eric BetzigJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. hessh@janelia.hhmi.org betzige@janelia.hhmi.org.ORCID 0000-0002-4192-1274
Harald F HessJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. hessh@janelia.hhmi.org betzige@janelia.hhmi.org.ORCID 0000-0003-3000-1533

Funding

Dynamics of Clathrin Coat Formation in CellsR01GM075252 · NIGMS · IMMUNE DISEASE INSTITUTE, INC. · PI KIRCHHAUSEN, TOMAS · 2005 to 2018
$4.6M
VISUALIZATION OF SUBCELLULAR DYNAMICS IN MULTICELLULAR ORGANISMSR35GM130386 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI TOMAS KIRCHHAUSEN · 2019 to 2026
$4.0M
Polarity Signals Coordinate Neuronal Migration and Germinal Zone ExitR01NS066936 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SOLECKI, DAVID JOSEPH · 2011 to 2021
$3.9M
Siah2: an E3 ligase organizes polarity and cytoskeletal links in neuron migrationR01NS104029 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SOLECKI, DAVID JOSEPH · 2018 to 2022
$2.0M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM075252NIGMS NIH HHS R35 GM130386NINDS NIH HHS R01 NS066936NINDS NIH HHS R01 NS104029
6 · The paper itself

Abstract

Within cells, the spatial compartmentalization of thousands of distinct proteins serves a multitude of diverse biochemical needs. Correlative super-resolution (SR) fluorescence and electron microscopy (EM) can elucidate protein spatial relationships to global ultrastructure, but has suffered from tradeoffs of structure preservation, fluorescence retention, resolution, and field of view. We developed a platform for three-dimensional cryogenic SR and focused ion beam-milled block-face EM across entire vitreously frozen cells. The approach preserves ultrastructure while enabling independent SR and EM workflow optimization. We discovered unexpected protein-ultrastructure relationships in mammalian cells including intranuclear vesicles containing endoplasmic reticulum-associated proteins, web-like adhesions between cultured neurons, and chromatin domains subclassified on the basis of transcriptional activity. Our findings illustrate the value of a comprehensive multimodal view of ultrastructural variability across whole cells.

Indexed as

AnimalsCell AdhesionCell Line, TumorCellsChlorocebus aethiopsCOS CellsCryoelectron MicroscopyFreezingHeLa CellsHumansImaging, Three-DimensionalMiceMicroscopy, Fluorescence

Identifiers

PMID31949053
PMCPMC7339343

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.