Circuit Design Features of a Stable Two-Cell System

Xu Zhou, Ruth A. Franklin, Miri Adler, Jeremy B. Jacox, Will Bailis, Justin A. Shyer, Richard A. Flavell, Avi Mayo, Uri Alon, Ruslan Medzhitov

Research output: Contribution to journalArticlepeer-review

Abstract

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. How is the cellular composition of a tissue stably maintained?

Original languageEnglish
Pages (from-to)744-757.e17
JournalCell
Volume172
Issue number4
DOIs
StatePublished - 8 Feb 2018

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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