A computational model of stem cell molecular mechanism to maintain tissue homeostasis

Stem cells, with their capacity to self-renew and to differentiate to more specialized cell types, play a key role to maintain homeostasis in adult tissues. To investigate how, in the dynamic stochastic environment of a tissue, non-genetic diversity and the precise balance between proliferation and...

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Bibliographic Details
Published in:PloS one 2020-07, Vol.15 (7), p.e0236519-e0236519
Main Authors: Khorasani, Najme, Sadeghi, Mehdi, Nowzari-Dalini, Abbas
Format: Article
Language:English
Subjects:
Aging
Biology and Life Sciences
Cell differentiation
Cell division
Cell growth
Cell self-renewal
Circuits
Computer and Information Sciences
Computer applications
Computer science
Decision making
Deoxyribonucleic acid
Differentiation
DNA
DNA biosynthesis
Gene expression
Genetic diversity
Genetic engineering
Homeostasis
Medicine and Health Sciences
Molecular modelling
Multiplication & division
Mutation
Noise
Ordinary differential equations
Physical Sciences
Population
Social Sciences
Stem cells
Stochasticity
Tissues
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Summary:Stem cells, with their capacity to self-renew and to differentiate to more specialized cell types, play a key role to maintain homeostasis in adult tissues. To investigate how, in the dynamic stochastic environment of a tissue, non-genetic diversity and the precise balance between proliferation and differentiation are achieved, it is necessary to understand the molecular mechanisms of the stem cells in decision making process. By focusing on the impact of stochasticity, we proposed a computational model describing the regulatory circuitry as a tri-stable dynamical system to reveal the mechanism which orchestrate this balance. Our model explains how the distribution of noise in genes, linked to the cell regulatory networks, affects cell decision-making to maintain homeostatic state. The noise effect on tissue homeostasis is achieved by regulating the probability of differentiation and self-renewal through symmetric and/or asymmetric cell divisions. Our model reveals, when mutations due to the replication of DNA in stem cell division, are inevitable, how mutations contribute to either aging gradually or the development of cancer in a short period of time. Furthermore, our model sheds some light on the impact of more complex regulatory networks on the system robustness against perturbations.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0236519