Evidence map›Paper›PMID 34226721›Full record

ArticleNature methods2021

SpaceM reveals metabolic states of single cells.

Luca Rappez, Mira Stadler, Sergio Triana, Rose Muthoni Gathungu, Katja Ovchinnikova, Prasad Phapale, Mathias Heikenwalder, Theodore Alexandrov

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
197citing papers in PubMed, 1 pooled it
19.9field-weighted citation impact, top 1% 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

197 citing papers in PubMed, 1 synthesis or guideline pooled it, 326 citations in OpenAlex.

  1. Pooled it
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  7. Peripheral GABA Signaling in Metabolic Adaptation and Maladaptation.International journal of molecular sciences · 2026
    Review
  8. PLANCK: super-multiplex optical imaging without labeling.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
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  11. Mass Spectrometry-Based Spatial Imaging of the Cochlea.Journal of the American Society for Mass Spectrometry · 2026
    Article
  12. New Analytical Technologies to Resolve, Interpret, and Understand Lipid Complexity.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026
    Review
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137 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 2 countries.

Luca Rappez *Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Mira Stadler *Institute of Chronic Inflammation and Cancer, Deutsches Krebs-Forschungszentrum (DKFZ), Heidelberg, Germany.
Sergio TrianaStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0370-7821
Rose Muthoni GathunguMetabolomics Core Facility, EMBL, Heidelberg, Germany.
Katja OvchinnikovaStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Prasad PhapaleMetabolomics Core Facility, EMBL, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-9487-597X
Mathias HeikenwalderInstitute of Chronic Inflammation and Cancer, Deutsches Krebs-Forschungszentrum (DKFZ), Heidelberg, Germany. m.heikenwaelder@dkfz-heidelberg.de.
Theodore AlexandrovStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. theodore.alexandrov@embl.de.ORCID http://orcid.org/0000-0001-9464-6125
Heidelberg University · DEEuropean Molecular Biology Organization · DEEuropean Molecular Biology Laboratory · DE

Funding

European Research Council 773089
6 · The paper itself

Abstract

A growing appreciation of the importance of cellular metabolism and revelations concerning the extent of cell-cell heterogeneity demand metabolic characterization of individual cells. We present SpaceM, an open-source method for in situ single-cell metabolomics that detects >100 metabolites from >1,000 individual cells per hour, together with a fluorescence-based readout and retention of morpho-spatial features. We validated SpaceM by predicting the cell types of cocultured human epithelial cells and mouse fibroblasts. We used SpaceM to show that stimulating human hepatocytes with fatty acids leads to the emergence of two coexisting subpopulations outlined by distinct cellular metabolic states. Inducing inflammation with the cytokine interleukin-17A perturbs the balance of these states in a process dependent on NF-κB signaling. The metabolic state markers were reproduced in a murine model of nonalcoholic steatohepatitis. We anticipate SpaceM to be broadly applicable for investigations of diverse cellular models and to democratize single-cell metabolomics.

Indexed as

AnimalsCoculture TechniquesEpithelial CellsFatty AcidsHepatocytesHumansImage Processing, Computer-AssistedInflammationInterleukin-17MaleMetabolomicsMiceMice, Inbred C57BLNF-kappa BNIH 3T3 CellsNon-alcoholic Fatty Liver DiseaseFatty AcidsIL17A protein, humanInterleukin-17NF-kappa B

Identifiers

PMID34226721
PMCPMC7611214
OpenAlexW3181434855

What OpenQuestion holds

Textmetadata
LicenceTDM
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.