Evidence map›Paper›PMID 41299044›Full record

ArticleNature biotechnology2025

All-optical visualization of specific molecules in the ultrastructural context of brain tissue.

Ons M'Saad, Allison Cairns, Jonathan Gulcicek, Ravi Kiran Kasula, Jacob Liao, Ilona Kondratiuk, Emma H Bewersdorf, Phylicia Kidd, Hanieh Falahati, Juliana E Gentile and 13 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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

29 citing papers in PubMed.

  1. Thousandfold Expansion Microscopy.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Heterogeneity of white-matter organization in the human brain.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Ons M'Saad *Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Allison Cairns *Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5766-1200
Jonathan GulcicekPanluminate Inc., New Haven, CT, USA.
Ravi Kiran KasulaDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Jacob LiaoDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0009-0003-5554-446X
Ilona KondratiukDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.
Emma H BewersdorfPanluminate Inc., New Haven, CT, USA.
Phylicia KiddDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Hanieh FalahatiDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Juliana E GentileDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8389-4489
Robert F NiescierDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Katherine WattersDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.
Robert C SternerDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-8195-4970
Seong-Il LeeDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Xiaojia GuoDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Xinran LiuDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Gary DesirDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Pietro De CamilliDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-9045-0723
James E RothmanDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Anthony J KoleskeDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Thomas BiedererDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.
Aaron T KuanDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA. aaron.kuan@yale.edu.ORCID http://orcid.org/0000-0002-1908-7949
Joerg BewersdorfDepartment of Cell Biology, Yale School of Medicine, New Haven, CT, USA. joerg.bewersdorf@yale.edu.ORCID http://orcid.org/0000-0002-4085-7020

Funding

Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI GERALD I SHULMAN · 1993 to 2026
$44.0M
Yale Cooperative Hematology Specialized Core CenterU54DK106857 · NIDDK · YALE UNIVERSITY · PI JOHN HWA, Diane S Krause · 2015 to 2026
$9.7M
MOLECULAR MECHANISMS IN SYNAPTIC VESICLE RECYCLINGR01NS036251 · NINDS · YALE UNIVERSITY · PI DE CAMILLI, PIETRO · 1997 to 2021
$4.7M
A 3D super-resolved platform for rapid and highly multiplexed proteomicsR44MH128999 · NIMH · PANLUMINATE INC. · PI M'SAAD, ONS · 2024 to 2025
$1.9M
The role of TRIO signaling in neuronal development, synaptic function, and circuit connectivityR56MH122449 · NIMH · YALE UNIVERSITY · PI CARDIN, JESSICA A, HIGLEY, MICHAEL JAMES · 2021 to 2022
$1.4M
Development of a sample preparation protocol for brain ultrastructural analysis, immunolabeling, and neuronal tracing by light microscopyR43MH128999 · NIMH · PANLUMINATE INC. · PI M'SAAD, ONS · 2022 to 2022
$249k
NIDDK NIH HHS P30 DK045735NIDDK NIH HHS U54 DK106857NINDS NIH HHS R01 NS036251ODCDC CDC HHS S10 OD020142U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH115939U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH124284U.S. Department of Health & Human Services | National Institutes of Health (NIH) NS036251U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01 DA01892U.S. Department of Health & Human Services | National Institutes of Health (NIH) R43MH128999U.S. Department of Health & Human Services | National Institutes of Health (NIH) R44MH128999U.S. Department of Health & Human Services | National Institutes of Health (NIH) R56MH122449Wellcome Trust (Wellcome) 203285/B/16/Z
6 · The paper itself

Abstract

Understanding the molecular anatomy and neural connectivity of the brain requires imaging technologies that can map the three-dimensional nanoscale distribution of specific proteins in the context of brain ultrastructure. Light and electron microscopy visualize either specific labels or anatomical ultrastructure but combining molecular specificity with anatomical context is challenging. Here we present pan-expansion microscopy of tissue (pan-ExM-t), an all-optical imaging method that combines ~16-24-fold linear expansion with fluorescent pan-stainings of proteins and lipids (providing electron microscopy-like ultrastructural context) and immunolabeling (for molecular imaging). We demonstrate the versatility of this approach by imaging synaptic and cell-specific antibodies in the ultrastructural three-dimensional context of presynaptic and postsynaptic densities, neuropil nanoarchitecture and cellular organelles in dissociated neuron cultures, and mouse brain tissue sections. Furthermore, we demonstrate tracing of neuronal circuitry from pan-ExM-t image volumes, suggesting that any laboratory with access to a confocal microscope can now localize specific molecules within nanoscale cellular and circuit contexts.

Identifiers

PMID41299044
PMCPMC13338931

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.