The landscape of cell–cell communication through single-cell transcriptomics
Open accessAbstract
Cell-cell communication is a fundamental process that shapes biological tissue. Historically, studies of cell-cell communication have been feasible for one or two cell types and a few genes. With the emergence of single-cell transcriptomics, we are now able to examine the genetic profiles of individual cells at unprecedented scale and depth. The availability of such data presents an exciting opportunity to construct a more comprehensive description of cell-cell communication. This review discusses the recent explosion of methods that have been developed to infer cell-cell communication from non-spatial and spatial single-cell transcriptomics, two promising technologies which have complementary strengths and limitations. We propose several avenues to propel this rapidly expanding field forward in meaningful ways.
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A considerable proportion of ligand-receptor interactions remains completely uncharacterised.
“Although many ligand-receptor (LR) interactions have been experimentally validated, a considerable proportion remains completely uncharacterised, reflecting the challenge to resolve intercellular communications networks [5], particularly within complex and heterogeneous tissue environments.”
From Quantitative profiling of lifespan-dependent cell-cell communication potential reveals dynamic ligand-receptor network shifts across mouse tissues (2026) · cites this paper as [5]
The 'Inferring CCC from single-cell genomics data' section discusses why transcriptomic methods can overestimate communication, and 'A summary of the different methods for CCC' refers to known ligand–receptor interactions. Neither states that a considerable proportion of ligand–receptor interactions is completely uncharacterised. Searches for uncharacterised interactions and incomplete ligand–receptor catalogs found no passage supporting that point; page numbers were not available in our copy. (LLM, conf=0.73)
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- Authors
- Almet, A. A., Cang, Z., Jin, S., & Nie, Q.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Nie, Qing
- Venue
- Current Opinion in Systems Biology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 26
- Pages
- 12-23
- ISSN
- 2452-3100 (ISSN-L)
- PMC
- PMC8104132
- OpenAlex
- W3146817258
- Cited by
- 197
- References
- 54
- Citations by year
- 2026: 34 · 2025: 38 · 2024: 37 · 2023: 49 · 2022: 30 · 2021: 9
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Systems Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Simons Foundation (594598)
- National Science Foundation (DMS1763272)
- National Institutes of Health (U01AR073159)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- intercellular communication, single-cell transcriptomics, spatial transcriptomics, cell-to-cell communication, tissue organization
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