Spatial correlations constrain cellular lifespan and pattern formation in corneal epithelium homeostasis

Author:

Strinkovsky Lior1ORCID,Havkin Evgeny1,Shalom-Feuerstein Ruby23,Savir Yonatan13ORCID

Affiliation:

1. Department of Physiology, Biophysics and System Biology, Faculty of Medicine, Technion, Haifa, Israel

2. Department of Genetics & Developmental Biology, Faculty of Medicine, Technion, Haifa, Israel

3. The Rappaport Family Institute for Research in the Medical Sciences, Technion, Haifa, Israel

Abstract

Homeostasis in adult tissues relies on the replication dynamics of stem cells, their progenitors and the spatial balance between them. This spatial and kinetic coordination is crucial to the successful maintenance of tissue size and its replenishment with new cells. However, our understanding of the role of cellular replicative lifespan and spatial correlation between cells in shaping tissue integrity is still lacking. We developed a mathematical model for the stochastic spatial dynamics that underlie the rejuvenation of corneal epithelium. Our model takes into account different spatial correlations between cell replication and cell removal. We derive the tradeoffs between replicative lifespan, spatial correlation length, and tissue rejuvenation dynamics. We determine the conditions that allow homeostasis and are consistent with biological timescales, pattern formation, and mutants phenotypes. Our results can be extended to any cellular system in which spatial homeostasis is maintained through cell replication.

Funder

American Federation for Aging Research

Israel Science Foundation

Rappaport Foundation

The Prince Center for Neurodegenerative Disorders of the Brain

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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