article published yes Bernat Corominas-Murtra author 43BE2298-F248-11E8-B48F-1D18A9856A870000-0001-9806-5643 Colinda L.G.J. Scheele author Kasumi Kishi author 3065DFC4-F248-11E8-B48F-1D18A9856A870000-0001-6060-4795 Saskia I.J. Ellenbroek author Benjamin D. Simons author Jacco Van Rheenen author Edouard B Hannezo author 3A9DB764-F248-11E8-B48F-1D18A9856A870000-0001-6005-1561 EdHa department Design Principles of Branching Morphogenesis project 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. https://research-explorer.ista.ac.at/download/8220/8223/2020_PNAS_Corominas.pdf application/pdfno National Academy of Sciences2020 eng 1091-6490 32611816 00055329290001410.1073/pnas.1921205117 1172916969-16975 https://ist.ac.at/en/news/order-from-noise/ Corominas-Murtra B, Scheele CLGJ, Kishi K, Ellenbroek SIJ, Simons BD, Van Rheenen J, Hannezo EB. 2020. Stem cell lineage survival as a noisy competition for niche access. Proceedings of the National Academy of Sciences of the United States of America. 117(29), 16969–16975. Corominas-Murtra B, Scheele CLGJ, Kishi K, et al. Stem cell lineage survival as a noisy competition for niche access. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2020;117(29):16969-16975. doi:<a href="https://doi.org/10.1073/pnas.1921205117">10.1073/pnas.1921205117</a> Corominas-Murtra, Bernat, Colinda L.G.J. Scheele, Kasumi Kishi, Saskia I.J. Ellenbroek, Benjamin D. Simons, Jacco Van Rheenen, and Edouard B Hannezo. “Stem Cell Lineage Survival as a Noisy Competition for Niche Access.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2020. <a href="https://doi.org/10.1073/pnas.1921205117">https://doi.org/10.1073/pnas.1921205117</a>. B. Corominas-Murtra <i>et al.</i>, “Stem cell lineage survival as a noisy competition for niche access,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 29. National Academy of Sciences, pp. 16969–16975, 2020. Corominas-Murtra, Bernat, et al. “Stem Cell Lineage Survival as a Noisy Competition for Niche Access.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 29, National Academy of Sciences, 2020, pp. 16969–75, doi:<a href="https://doi.org/10.1073/pnas.1921205117">10.1073/pnas.1921205117</a>. Corominas-Murtra, B., Scheele, C. L. G. J., Kishi, K., Ellenbroek, S. I. J., Simons, B. D., Van Rheenen, J., &#38; Hannezo, E. B. (2020). Stem cell lineage survival as a noisy competition for niche access. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1921205117">https://doi.org/10.1073/pnas.1921205117</a> B. Corominas-Murtra, C.L.G.J. Scheele, K. Kishi, S.I.J. Ellenbroek, B.D. Simons, J. Van Rheenen, E.B. Hannezo, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 16969–16975. 82202020-08-09T22:00:52Z2026-04-03T09:29:04Z