Evidence map›Paper›PMID 39103318›Full record

ArticleNature communications2024

Multiplexed volumetric CLEM enabled by scFvs provides insights into the cytology of cerebellar cortex.

Xiaomeng Han, Xiaotang Lu, Peter H Li, Shuohong Wang, Richard Schalek, Yaron Meirovitch, Zudi Lin, Jason Adhinarta, Karl D Murray, Leah M MacNiven and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Xiaomeng HanDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA. xiaomenghan@fas.harvard.edu.ORCID 0000-0002-1409-7419
Xiaotang LuDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA. xiaotang_lu@fas.harvard.edu.ORCID 0000-0002-8575-5394
Peter H LiGoogle Research, Mountain View, CA, USA.ORCID 0000-0001-6193-4454
Shuohong WangDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Richard SchalekDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Yaron MeirovitchDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Zudi LinSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.ORCID 0000-0003-4176-8035
Jason AdhinartaComputer Science Department, Boston College, Chestnut Hill, MA, USA.ORCID 0000-0002-6247-7475
Karl D MurrayDepartment of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA, USA.
Leah M MacNivenDepartment of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA, USA.
Daniel R BergerDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.ORCID 0000-0002-9677-6932
Yuelong WuDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.ORCID 0000-0003-0075-1237
Tao FangProgram of Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0001-8129-8635
Elif Sevde MeralBezmialem Vakif University School of Medicine, Istanbul, Turkey.ORCID 0009-0008-3336-3293
Shadnan AsrafSchool of Public Health, University of Massachusetts Amherst, Amherst, MA, USA.
Hidde PloeghProgram of Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0002-1090-6071
Hanspeter PfisterDepartment of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA, USA.
Donglai WeiComputer Science Department, Boston College, Chestnut Hill, MA, USA.
Viren JainGoogle Research, Mountain View, CA, USA.ORCID 0000-0003-1488-3505
James S TrimmerDepartment of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA, USA.ORCID 0000-0002-6117-3912
Jeff W LichtmanDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA. jeff@mcb.harvard.edu.ORCID 0000-0002-0208-3212

Funding

Zooming into the fish's brain-What is really going on! Connectomics analysis of larval zebrafish.U19NS104653 · NINDS · HARVARD UNIVERSITY · PI JOSHUA T VOGELSTEIN · 2017 to 2026
$39.4M
Res Support CoreP50MH094271 · NIMH · HARVARD UNIVERSITY · PI ARLOTTA, PAOLA · 2011 to 2022
$18.6M
Recombinant Immunolabels for Nanoprecise Brain Mapping Across ScalesU24NS109113 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KARL Daniel MURRAY · 2018 to 2026
$9.9M
A Tool for Synapse-level Circuit Analysis of Human Cerebral Cortex Specimens.UG3MH123386 · NIMH · HARVARD UNIVERSITY · PI LICHTMAN, JEFF W · 2021 to 2023
$2.4M
New Methodologies for ConnectomicsK99MH128891 · NIMH · HARVARD UNIVERSITY · PI LU, XIAOTANG · 2022 to 2023
$266k
NIMH NIH HHS K99 MH128891NIMH NIH HHS P50 MH094271NIMH NIH HHS UG3 MH123386NINDS NIH HHS U19 NS104653NINDS NIH HHS U24 NS109113
6 · The paper itself

Abstract

Mapping neuronal networks is a central focus in neuroscience. While volume electron microscopy (vEM) can reveal the fine structure of neuronal networks (connectomics), it does not provide molecular information to identify cell types or functions. We developed an approach that uses fluorescent single-chain variable fragments (scFvs) to perform multiplexed detergent-free immunolabeling and volumetric-correlated-light-and-electron-microscopy on the same sample. We generated eight fluorescent scFvs targeting brain markers. Six fluorescent probes were imaged in the cerebellum of a female mouse, using confocal microscopy with spectral unmixing, followed by vEM of the same sample. The results provide excellent ultrastructure superimposed with multiple fluorescence channels. Using this approach, we documented a poorly described cell type, two types of mossy fiber terminals, and the subcellular localization of one type of ion channel. Because scFvs can be derived from existing monoclonal antibodies, hundreds of such probes can be generated to enable molecular overlays for connectomic studies.

Indexed as

Cerebellar CortexAnimalsConnectomeCytodiagnosisFemaleFluorescent DyesMiceMice, Inbred C57BLMicroscopy, ConfocalMicroscopy, ElectronNeuronsFluorescent Dyes

Identifiers

PMID39103318
PMCPMC11300613

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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.