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Stem cell lineage survival as a noisy competition for niche access.

Accepted version
Peer-reviewed

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Authors

Corominas-Murtra, Bernat 
Scheele, Colinda LGJ  ORCID logo  https://orcid.org/0000-0001-8999-5451
Kishi, Kasumi 
Ellenbroek, Saskia IJ  ORCID logo  https://orcid.org/0000-0001-8007-2634

Abstract

Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a common ("universal") functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We test the predictions of this theory on datasets of pubertal mammary gland tips and embryonic kidney tips, as well as homeostatic intestinal crypts. Importantly, we find good agreement for the predicted functional dependency of the competition as a function of position, and thus functional stem cell number in each organ. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics, and we discuss the applicability of this theory to other settings.

Description

Keywords

biophysical modeling, intestinal renewal, mammary morphogenesis, stem cell dynamics, stochastic processes, Animals, Cell Lineage, Cell Self Renewal, Cell Survival, Female, Homeostasis, Intestines, Kidney, Mammary Glands, Animal, Mice, Models, Theoretical, Signal-To-Noise Ratio, Stem Cell Niche, Stem Cells

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

117

Publisher

Proceedings of the National Academy of Sciences

Rights

All rights reserved
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
Wellcome Trust Royal Society