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Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation

Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation
Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation

To maintain renewing epithelial tissues in a healthy, homeostatic state, cell divisions and differentiation need to be tightly regulated. Mechanisms of homeostatic regulation often rely on crowding feedback control: cells are able to sense the cell density in their environment, via various molecular and mechanosensing pathways, and respond by adjusting division, differentiation, and cell state transitions appropriately. Here, we determine, via a mathematically rigorous framework, which general conditions for the crowding feedback regulation (i) must be minimally met, and (ii) are sufficient, to allow the maintenance of homeostasis in renewing tissues. We show that those conditions naturally allow for a degree of robustness toward disruption of regulation. Furthermore, intrinsic to this feedback regulation is that stem cell identity is established collectively by the cell population, not by individual cells, which implies the possibility of ‘quasi-dedifferentiation’, in which cells committed to differentiation may reacquire stem cell properties upon depletion of the stem cell pool. These findings can guide future experimental campaigns to identify specific crowding feedback mechanisms.

Dedifferentiation, Feedback control, Homeostasis, Robustness, Stability, Stem cells, Tissue cell population dynamics
0303-6812
Parigini, Cristina
e703096b-49c9-43e6-af7c-62a3a85e9a9b
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Parigini, Cristina
e703096b-49c9-43e6-af7c-62a3a85e9a9b
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9

Parigini, Cristina and Greulich, Philip (2024) Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation. Journal of Mathematical Biology, 88 (4), [47]. (doi:10.1007/s00285-024-02057-0).

Record type: Article

Abstract

To maintain renewing epithelial tissues in a healthy, homeostatic state, cell divisions and differentiation need to be tightly regulated. Mechanisms of homeostatic regulation often rely on crowding feedback control: cells are able to sense the cell density in their environment, via various molecular and mechanosensing pathways, and respond by adjusting division, differentiation, and cell state transitions appropriately. Here, we determine, via a mathematically rigorous framework, which general conditions for the crowding feedback regulation (i) must be minimally met, and (ii) are sufficient, to allow the maintenance of homeostasis in renewing tissues. We show that those conditions naturally allow for a degree of robustness toward disruption of regulation. Furthermore, intrinsic to this feedback regulation is that stem cell identity is established collectively by the cell population, not by individual cells, which implies the possibility of ‘quasi-dedifferentiation’, in which cells committed to differentiation may reacquire stem cell properties upon depletion of the stem cell pool. These findings can guide future experimental campaigns to identify specific crowding feedback mechanisms.

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Accepted/In Press date: 28 January 2024
e-pub ahead of print date: 23 March 2024
Published date: 23 March 2024
Additional Information: © 2024. The Author(s).
Keywords: Dedifferentiation, Feedback control, Homeostasis, Robustness, Stability, Stem cells, Tissue cell population dynamics

Identifiers

Local EPrints ID: 488917
URI: http://eprints.soton.ac.uk/id/eprint/488917
ISSN: 0303-6812
PURE UUID: 2f37e78e-0c4b-4497-ba9e-ce45e883804b
ORCID for Philip Greulich: ORCID iD orcid.org/0000-0001-5247-6738

Catalogue record

Date deposited: 09 Apr 2024 16:41
Last modified: 14 May 2024 01:45

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Contributors

Author: Cristina Parigini
Author: Philip Greulich ORCID iD

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