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Metabolomics across scales: from single cells to population studies | Nature
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Summary
Article ADS CAS PubMed PubMed Central Google Scholar Castro, D. Article ADS CAS PubMed PubMed Central Google Scholar Cairns, J. Article ADS CAS PubMed PubMed Central Google Scholar Christofk, H. et al. Article ADS CAS PubMed PubMed Central Google Scholar Buglakova, E. et al.
## Summary
Article ADS CAS PubMed PubMed Central Google Scholar Castro, D. Article ADS CAS PubMed PubMed Central Google Scholar Cairns, J. Article ADS CAS PubMed PubMed Central Google Scholar Christofk, H. et al. Article ADS CAS PubMed PubMed Central Google Scholar Buglakova, E. et al.
## Article Content
Subjects
Metabolomics
Abstract
Metabolomics has matured into a powerful approach for probing metabolism, offering readouts that closely reflect cellular and organismal function in health and disease. Here we highlight two rapidly advancing frontiers: single-cell metabolomics and population-scale metabolomics. Single-cell metabolomics resolves the metabolic states of individual cells, uncovering cell-to-cell heterogeneity and spatial organization within tissues. Population-scale profiling profiles metabolites across large cohorts, enabling the discovery of markers of disease, environmental exposures and genetic variation. Although these approaches operate at different scales, they face shared challenges—including metabolite identification, quantification and multimodal data integration—and offer common advantages, such as the ability to capture non-genetic influences on phenotype and to scale to high throughput. We propose that continued advances in scalability will bring these domains together, enabling the construction of comprehensive metabolic atlases that chart cellular and interindividual variation and provide training data for foundation models of metabolism. By integrating cellular and population-level insights, single-cell and population-scale metabolomics promise to advance our understanding of metabolism across biology, medicine and pharmacology.
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Fig. 1: Single-cell metabolomics and population-scale metabolomics.
Fig. 2: Bridging metabolomics across scales: from single cells to population studies.
References
Johnson, C. H., Ivanisevic, J. & Siuzdak, G. Metabolomics: beyond biomarkers and towards mechanisms.
Nat. Rev. Mol. Cell Biol.
17
, 451–459 (2016).
Article
CAS
PubMed
PubMed Central
Google Scholar
Wellen, K. E. & Thompson, C. B. A two-way street: reciprocal regulation of metabolism and signalling.
Nat. Rev. Mol. Cell Biol.
13
, 270–276 (2012).
Article
CAS
PubMed
Google Scholar
Baker, S. A. & Rutter, J. Metabolites as signalling molecules.
Nat. Rev. Mol. Cell Biol.
24
, 355–374 (2023).
Article
CAS
PubMed
Google Scholar
Zamboni, N., Saghatelian, A. & Patti, G. J. Defining the metabolome: size, flux, and regulation.
Mol. Cell
58
, 699–706 (2015).
Article
CAS
PubMed
PubMed Central
Google Scholar
Jang, C., Chen, L. & Rabinowitz, J. D. Metabolomics and isotope tracing.
Cell
173
, 822–837 (2018).
Article
CAS
PubMed
PubMed Central
Google Scholar
Bloszies, C. S. & Fiehn, O. Using untargeted metabolomics for detecting exposome compounds.
Curr. Opin. Toxicol.
8
, 87–92 (2018).
Article
Google Scholar
Wishart, D. S. Emerging applications of metabolomics in drug discovery and precision medicine.
Nat. Rev. Drug Discov.
15
, 473–484 (2016).
Article
CAS
PubMed
Google Scholar
Saigusa, D., Matsukawa, N., Hishinuma, E. & Koshiba, S. Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics.
Drug Metab. Pharmacokinet.
37
, 100373 (2021).
Article
CAS
PubMed
Google Scholar
Pang, H. & Hu, Z. Metabolomics in drug research and development: the recent advances in technologies and applications.
Acta Pharm. Sin. B
13
, 3238–3251 (2023).
Article
CAS
PubMed
PubMed Central
Google Scholar
Kirwan, J. A. Translating metabolomics into clinical practice.
Nat. Rev. Bioeng.
1
, 228–229 (2023).
Article
CAS
Google Scholar
Schuhknecht, L. et al. A human metabolic map of pharmacological perturbations reveals drug modes of action.
Nat. Biotechnol.
43
, 1996–2008 (2025).
A large-scale study focusing on how metabolomics can reveal the metabolic mode of action of drugs.
Article
CAS
PubMed
Google Scholar
Ali, A. et al. Single-cell metabolomics by mass spectrometry: advances, challenges, and future applications.
Trends Anal. Chem.
120
, 115436 (2019).
Article
Google Scholar
Saunders, K. D. G., Lewis, H.-M., Beste, D. J. V., Cexus, O. & Bailey, M. J. Spatial single cell metabolomics: current challenges and future developments.
Curr. Opin. Chem. Biol.
75
, 102327 (2023).
Article
CAS
PubMed
Google Scholar
Petrova, B. & Guler, A. T. Recent developments in single-cell metabolomics by mass Spectrometry─A perspective.
J. Proteome Res.
24
, 1493–1518 (2025).
Article
CAS
PubMed
Google Scholar
Hajjar, G. et al. Scaling-up metabolomics: current state and perspectives.
Trends Anal. Chem.
167
, 117225 (2023).
Article
CAS
Google Scholar
Plekhova, V., De Windt, K., De Spieg
---
## Expert Analysis
### Merits
- We propose that continued advances in scalability will bring these domains together, enabling the construction of comprehensive metabolic atlases that chart cellular and interindividual variation and provide training data for foundation models of metabolism.
### Areas for Consideration
N/A
### Implications
- We propose that continued advances in scalability will bring these domains together, enabling the construction of comprehensive metabolic atlases that chart cellular and interindividual variation and provide training data for foundation models of metabolism.
- Go to natureasia.com Buy this article Purchase on SpringerLink Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Fig. 1: Single-cell metabolomics and population-scale metabolomics.
- A two-way street: reciprocal regulation of metabolism and signalling.
- Defining the metabolome: size, flux, and regulation.
### Expert Commentary
This article covers pubmed, article, google topics. Notable strengths include discussion of pubmed. Readability: Flesch-Kincaid grade 0.0. Word count: 2175.
Article ADS CAS PubMed PubMed Central Google Scholar Castro, D. Article ADS CAS PubMed PubMed Central Google Scholar Cairns, J. Article ADS CAS PubMed PubMed Central Google Scholar Christofk, H. et al. Article ADS CAS PubMed PubMed Central Google Scholar Buglakova, E. et al.
## Article Content
Subjects
Metabolomics
Abstract
Metabolomics has matured into a powerful approach for probing metabolism, offering readouts that closely reflect cellular and organismal function in health and disease. Here we highlight two rapidly advancing frontiers: single-cell metabolomics and population-scale metabolomics. Single-cell metabolomics resolves the metabolic states of individual cells, uncovering cell-to-cell heterogeneity and spatial organization within tissues. Population-scale profiling profiles metabolites across large cohorts, enabling the discovery of markers of disease, environmental exposures and genetic variation. Although these approaches operate at different scales, they face shared challenges—including metabolite identification, quantification and multimodal data integration—and offer common advantages, such as the ability to capture non-genetic influences on phenotype and to scale to high throughput. We propose that continued advances in scalability will bring these domains together, enabling the construction of comprehensive metabolic atlases that chart cellular and interindividual variation and provide training data for foundation models of metabolism. By integrating cellular and population-level insights, single-cell and population-scale metabolomics promise to advance our understanding of metabolism across biology, medicine and pharmacology.
Access through your institution
Buy or subscribe
This is a preview of subscription content,
access via your institution
Access options
Access through your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
27,99 €
/ 30 days
cancel any time
Learn more
Subscription info for Korean customers
We have a dedicated website for our Korean customers. Please go to
natureasia.com
to subscribe to this journal.
Go to natureasia.com
Buy this article
Purchase on SpringerLink
Instant access to the full article PDF.
39,95 €
Prices may be subject to local taxes which are calculated during checkout
Fig. 1: Single-cell metabolomics and population-scale metabolomics.
Fig. 2: Bridging metabolomics across scales: from single cells to population studies.
References
Johnson, C. H., Ivanisevic, J. & Siuzdak, G. Metabolomics: beyond biomarkers and towards mechanisms.
Nat. Rev. Mol. Cell Biol.
17
, 451–459 (2016).
Article
CAS
PubMed
PubMed Central
Google Scholar
Wellen, K. E. & Thompson, C. B. A two-way street: reciprocal regulation of metabolism and signalling.
Nat. Rev. Mol. Cell Biol.
13
, 270–276 (2012).
Article
CAS
PubMed
Google Scholar
Baker, S. A. & Rutter, J. Metabolites as signalling molecules.
Nat. Rev. Mol. Cell Biol.
24
, 355–374 (2023).
Article
CAS
PubMed
Google Scholar
Zamboni, N., Saghatelian, A. & Patti, G. J. Defining the metabolome: size, flux, and regulation.
Mol. Cell
58
, 699–706 (2015).
Article
CAS
PubMed
PubMed Central
Google Scholar
Jang, C., Chen, L. & Rabinowitz, J. D. Metabolomics and isotope tracing.
Cell
173
, 822–837 (2018).
Article
CAS
PubMed
PubMed Central
Google Scholar
Bloszies, C. S. & Fiehn, O. Using untargeted metabolomics for detecting exposome compounds.
Curr. Opin. Toxicol.
8
, 87–92 (2018).
Article
Google Scholar
Wishart, D. S. Emerging applications of metabolomics in drug discovery and precision medicine.
Nat. Rev. Drug Discov.
15
, 473–484 (2016).
Article
CAS
PubMed
Google Scholar
Saigusa, D., Matsukawa, N., Hishinuma, E. & Koshiba, S. Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics.
Drug Metab. Pharmacokinet.
37
, 100373 (2021).
Article
CAS
PubMed
Google Scholar
Pang, H. & Hu, Z. Metabolomics in drug research and development: the recent advances in technologies and applications.
Acta Pharm. Sin. B
13
, 3238–3251 (2023).
Article
CAS
PubMed
PubMed Central
Google Scholar
Kirwan, J. A. Translating metabolomics into clinical practice.
Nat. Rev. Bioeng.
1
, 228–229 (2023).
Article
CAS
Google Scholar
Schuhknecht, L. et al. A human metabolic map of pharmacological perturbations reveals drug modes of action.
Nat. Biotechnol.
43
, 1996–2008 (2025).
A large-scale study focusing on how metabolomics can reveal the metabolic mode of action of drugs.
Article
CAS
PubMed
Google Scholar
Ali, A. et al. Single-cell metabolomics by mass spectrometry: advances, challenges, and future applications.
Trends Anal. Chem.
120
, 115436 (2019).
Article
Google Scholar
Saunders, K. D. G., Lewis, H.-M., Beste, D. J. V., Cexus, O. & Bailey, M. J. Spatial single cell metabolomics: current challenges and future developments.
Curr. Opin. Chem. Biol.
75
, 102327 (2023).
Article
CAS
PubMed
Google Scholar
Petrova, B. & Guler, A. T. Recent developments in single-cell metabolomics by mass Spectrometry─A perspective.
J. Proteome Res.
24
, 1493–1518 (2025).
Article
CAS
PubMed
Google Scholar
Hajjar, G. et al. Scaling-up metabolomics: current state and perspectives.
Trends Anal. Chem.
167
, 117225 (2023).
Article
CAS
Google Scholar
Plekhova, V., De Windt, K., De Spieg
---
## Expert Analysis
### Merits
- We propose that continued advances in scalability will bring these domains together, enabling the construction of comprehensive metabolic atlases that chart cellular and interindividual variation and provide training data for foundation models of metabolism.
### Areas for Consideration
N/A
### Implications
- We propose that continued advances in scalability will bring these domains together, enabling the construction of comprehensive metabolic atlases that chart cellular and interindividual variation and provide training data for foundation models of metabolism.
- Go to natureasia.com Buy this article Purchase on SpringerLink Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Fig. 1: Single-cell metabolomics and population-scale metabolomics.
- A two-way street: reciprocal regulation of metabolism and signalling.
- Defining the metabolome: size, flux, and regulation.
### Expert Commentary
This article covers pubmed, article, google topics. Notable strengths include discussion of pubmed. Readability: Flesch-Kincaid grade 0.0. Word count: 2175.
pubmed
article
google
scholar
cas
cell
central
metabolomics
Original Source
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