Open AccessA computational model of stem cell molecular mechanism to maintain tissue homeostasis
Author(s) -
Nematollah Khorasani,
Mehdi Sadeghi,
Abbas Nowzari-Dalini
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0236519
Subject(s) - stem cell , biology , microbiology and biotechnology , mechanism (biology) , cellular differentiation , robustness (evolution) , microrna , homeostasis , systems biology , cell division , cell , computational biology , genetics , gene , philosophy , epistemology
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.