Evidence map›Paper›PMID 34330905›Full record

ArticleNature communications2021

Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging.

Xavier Rovira-Clavé, Sizun Jiang, Yunhao Bai, Bokai Zhu, Graham Barlow, Salil Bhate, Ahmet F Coskun, Guojun Han, Chin-Min Kimmy Ho, Chuck Hitzman and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.2field-weighted citation impact, top 4% of its field
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

46 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Living single-cell metabolomicsChemical science · 2026
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  10. Mass Spectrometry Imaging.Analytical chemistry · 2025
    Review
  11. Article
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  13. Review
  14. Spatial-Omics Methods and Applications.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  15. Article
  16. Review
  17. Tool to Resolve Distortions in Elemental and Isotopic Imaging.Journal of the American Chemical Society · 2024
    Article
  18. Review
  19. Multiplex protein imaging in tumour biology.Nature reviews. Cancer · 2024
    Review
  20. Review
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

13 authors at 4 institutions in 2 countries.

Xavier Rovira-Clavé *Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Sizun Jiang *Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6149-3142
Yunhao BaiDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Bokai ZhuDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Graham BarlowDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-9335-5414
Salil BhateDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Ahmet F CoskunDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-5797-1524
Guojun HanDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-2621-3595
Chin-Min Kimmy HoDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-7994-0630
Chuck HitzmanStanford Nano Shared Facility, Stanford University, Stanford, CA, USA.
Shih-Yu ChenDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Felice-Alessio BavaDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Garry P NolanDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA. gnolan@stanford.edu.ORCID 0000-0002-8862-9043
Stanford University · USInstitute of Biomedical Sciences, Academia Sinica · TWInstitute of Plant and Microbial Biology, Academia Sinica · TWStanford Medicine · US

Funding

Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
High-throughput sequencer for multi-scale genomic studiesS10OD020141 · OD · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2015 to 2015
$600k
Spatial Epigenomic Profiling of Immune Cell Signatures at Subcellular Resolution in Health and DiseaseK25AI140783 · NIAID · STANFORD UNIVERSITY · PI COSKUN, AHMET F. · 2018 to 2022
$539k
NIAID NIH HHS K25 AI140783NIDDK NIH HHS P30 DK116074NIH HHS S10 OD020141
6 · The paper itself

Abstract

Simultaneous visualization of the relationship between multiple biomolecules and their ligands or small molecules at the nanometer scale in cells will enable greater understanding of how biological processes operate. We present here high-definition multiplex ion beam imaging (HD-MIBI), a secondary ion mass spectrometry approach capable of high-parameter imaging in 3D of targeted biological entities and exogenously added structurally-unmodified small molecules. With this technology, the atomic constituents of the biomolecules themselves can be used in our system as the "tag" and we demonstrate measurements down to ~30 nm lateral resolution. We correlated the subcellular localization of the chemotherapy drug cisplatin simultaneously with five subnuclear structures. Cisplatin was preferentially enriched in nuclear speckles and excluded from closed-chromatin regions, indicative of a role for cisplatin in active regions of chromatin. Unexpectedly, cells surviving multi-drug treatment with cisplatin and the BET inhibitor JQ1 demonstrated near total cisplatin exclusion from the nucleus, suggesting that selective subcellular drug relocalization may modulate resistance to this important chemotherapeutic treatment. Multiplexed high-resolution imaging techniques, such as HD-MIBI, will enable studies of biomolecules and drug distributions in biologically relevant subcellular microenvironments by visualizing the processes themselves in concert, rather than inferring mechanism through surrogate analyses.

Indexed as

Antineoplastic AgentsAzepinesCell Line, TumorCell NucleusCisplatinCytoplasmHeLa CellsHumansIntracellular SpaceJurkat CellsMicroscopy, ConfocalSpectrometry, Mass, Secondary IonTriazolesAntineoplastic AgentsAzepinesCisplatin(+)-JQ1 compoundTriazoles

Identifiers

PMID34330905
PMCPMC8324837
OpenAlexW3186815057

What OpenQuestion holds

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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.