{"title":"Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation.","authors":"Cristina Parigini, Philip Greulich","doi":"10.1007/s00285-024-02057-0","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":50148,"journal":{"name":"Journal of Mathematical Biology","volume":"88 4","pages":"47"},"PeriodicalIF":2.2000,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960778/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Mathematical Biology","FirstCategoryId":"100","ListUrlMain":"https://doi.org/10.1007/s00285-024-02057-0","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
The Journal of Mathematical Biology focuses on mathematical biology - work that uses mathematical approaches to gain biological understanding or explain biological phenomena.
Areas of biology covered include, but are not restricted to, cell biology, physiology, development, neurobiology, genetics and population genetics, population biology, ecology, behavioural biology, evolution, epidemiology, immunology, molecular biology, biofluids, DNA and protein structure and function. All mathematical approaches including computational and visualization approaches are appropriate.