PT  - JOURNAL ARTICLE
AU  - Bernat Corominas-Murtra
AU  - Colinda L.G.J. Scheele
AU  - Kasumi Kishi
AU  - Saskia I.J. Ellenbroek
AU  - Benjamin D. Simons
AU  - Jacco van Rheenen
AU  - Edouard Hannezo
TI  - Stem cell lineage survival as a noisy competition for niche access
AID  - 10.1101/2020.02.12.945253
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.12.945253
4099  - http://biorxiv.org/content/early/2020/02/12/2020.02.12.945253.short
4100  - http://biorxiv.org/content/early/2020/02/12/2020.02.12.945253.full
AB  - 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 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 favourably repositioned. Importantly, even when assuming that all cells in a tissue molecularly equivalent, the model predicts a common (“universal”) functional dependence of the long-term clonal survival probability on the position within 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 on pubertal mammary gland tips, embryonic kidney tips as well homeostatic intestinal crypt, and find good quantitative agreement for the number of functional stem cells in each organ, as well as the predicted functional dependence of the competition.