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Updated: Sep 24, 2025
09:56
Mapping the Emergent Spatial Organization of Mammalian Cells using Micropatterns and Quantitative Imaging
Published on: April 30, 2019
6.7K
Spatial dynamics of feedback and feedforward regulation in cell lineages
Peter Uhl1,2, John Lowengrub3, Natalia Komarova3
1Department of Mathematics and Statistics, San Diego State University, San Diego, California, United States of America.
Plos Computational Biology
|May 6, 2022
Summary
Tissue homeostasis relies on cell feedback loops. Spatial models show negative feedback alone fails, but combining it with a feedforward loop can achieve stability.
Area of Science:
- Cell biology
- Mathematical modeling
- Tissue homeostasis
Background:
- Cell lineages are crucial for tissue homeostasis.
- Negative feedback from differentiated cells on stem cell self-renewal was hypothesized to maintain homeostasis in well-mixed models.
- Spatial structure in cell dynamics may alter these feedback mechanisms.
Purpose of the Study:
- To investigate cell lineage dynamics using spatially explicit computational models.
- To determine if negative feedback alone can maintain tissue homeostasis under spatial constraints.
- To explore combinations of feedback and feedforward mechanisms for achieving homeostasis.
Main Methods:
- Development of spatially explicit computational models.
- Simulation of cell division, differentiation, death, and migration/diffusion.
- Analysis of negative feedback loops on stem cell self-renewal probability.
- Inclusion of spatial feedforward loops involving stem and transit amplifying cells.
Main Results:
- Negative feedback alone failed to maintain homeostasis under strong spatial restrictions and fast migration.
- Negative feedback regulated cell density and promoted spatial structure formation.
- Combining spatially restricted negative feedback with a spatial feedforward loop successfully achieved tissue homeostasis.
Conclusions:
- Simple negative feedback is insufficient for maintaining tissue homeostasis in spatially structured cell lineages.
- Tissue homeostasis requires complex regulatory dynamics, likely involving combinations of spatially explicit feedback and feedforward mechanisms.
- Spatial organization plays a critical role in cell lineage regulation and tissue stability.
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