Cellular population dynamics control the robustness of the stem cell niche.
File(s)
Published version
Author(s)
MacLean, AL
Kirk, PD
Stumpf, MP
Type
Journal Article
Abstract
Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain 'stemness' through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell-niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly) high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell-cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche - and hence of the stem cell pool in the niche - depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.
Date Issued
2015-10-09
Date Acceptance
2015-09-14
Citation
Biology Open, 2015, 4 (11), pp.1420-1426
ISSN
2046-6390
Publisher
Company of Biologists
Start Page
1420
End Page
1426
Journal / Book Title
Biology Open
Volume
4
Issue
11
Copyright Statement
This is an Open Access article distributed under the terms of the Creative Commons Attribution
License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution and reproduction in any medium provided that the original work is properly attributed.
License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution and reproduction in any medium provided that the original work is properly attributed.
License URL
Identifier
PII: bio.013714
Subjects
Asymmetric division
Cell fate
Self-renewal
Stability analysis
Stem cell niche
Publication Status
Published