Circuit Design Features of a Stable Two-Cell System
Open accessAbstract
Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit with specific properties that ensure homeostasis. Here, we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. Analytical screening of all possible two-cell circuit topologies revealed the circuit features sufficient for stability, including environmental constraint and negative-feedback regulation. Moreover, we found that cell-cell contact is essential for the stability of the macrophage-fibroblast circuit. These findings illustrate principles of cell circuit design and provide a quantitative perspective on cell interactions.
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The αv-containing integrins αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8 bind to the latency-associated peptide (LAP) of TGF-β1.
“the integrins αvβ1, αvβ3, αvβ5, αvβ6 and αvβ8 have all been shown to bind to an N-terminal fragment of the TGFβ1 gene product called the latency associated peptide (LAP)”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [92]
LAP normally forms a noncovalent latent complex with active TGF-β, preventing TGF-β from binding its receptors and inducing biological effects.
“which normally forms a noncovalent complex (latent complex) with the active cytokine, preventing TGF-β from binding to its cognate receptors and inducing biological effects89–93”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [92]
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- Authors
- Zhou, X., Franklin, R. A., Adler, M., Jacox, J. B., Bailis, W., Shyer, J. A., Flavell, R. A., Mayo, A., Alon, U., & Medzhitov, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Weizmann Institute of Science (IL)
- Corresponding author
- Alon, Uri
- Medzhitov, Ruslan
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 172
- Issue
- 4
- Pages
- 744-757.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7377352
- OpenAlex
- W2785854718
- Cited by
- 430
- References
- 53
- Citations by year
- 2026: 61 · 2025: 61 · 2024: 59 · 2023: 66 · 2022: 57 · 2021: 37 · 2020: 40 · 2019: 33 · 2018: 16
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Blavatnik Family Foundation
- Else Kroner-Fresenius Foundation
- Scleroderma Research Foundation
- Biogen
- Howard Hughes Medical Institute
- Jane Coffin Childs Memorial Fund
- CRI Donald Gogel
- NIH (T32GM007205, F31AI133855)
- NRSA NCI (1F30CA189926-01)
- CRI Irvington
- HHMI
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- macrophage-fibroblast interaction, paracrine signaling, circuit stability, robustness to disturbances, negative feedback regulation, cell-cell contact, tissue homeostasis, intercellular communication, circuit topology
- MeSH terms
- Animals, Cell Communication, Cell Survival, Female, Fibroblasts, Macrophages, Male, Mice, Transgenic, Cell Proliferation, Mice
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