{"pmid":1,"file":[{"content_type":"application/pdf","success":1,"date_updated":"2020-08-10T06:50:28Z","creator":"dernst","file_id":"8223","file_name":"2020_PNAS_Corominas.pdf","access_level":"open_access","date_created":"2020-08-10T06:50:28Z","file_size":1111604,"relation":"main_file"}],"publisher":"National Academy of Sciences","day":"21","department":[{"_id":"EdHa"}],"isi":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","file_date_updated":"2020-08-10T06:50:28Z","abstract":[{"lang":"eng","text":"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."}],"volume":117,"date_created":"2020-08-09T22:00:52Z","publication_status":"published","publication":"Proceedings of the National Academy of Sciences of the United States of America","language":[{"iso":"eng"}],"scopus_import":"1","_id":"8220","oa":1,"intvolume":"       117","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"citation":{"chicago":"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>.","apa":"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>","ista":"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.","mla":"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>.","short":"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.","ieee":"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.","ama":"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>"},"date_published":"2020-07-21T00:00:00Z","title":"Stem cell lineage survival as a noisy competition for niche access","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/order-from-noise/"}]},"quality_controlled":"1","project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E"}],"publication_identifier":{"eissn":["10916490"]},"month":"07","ec_funded":1,"year":"2020","oa_version":"Published Version","date_updated":"2023-08-22T08:29:30Z","external_id":{"pmid":["32611816"],"isi":["000553292900014"]},"status":"public","author":[{"first_name":"Bernat","orcid":"0000-0001-9806-5643","last_name":"Corominas-Murtra","full_name":"Corominas-Murtra, Bernat","id":"43BE2298-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Scheele, Colinda L.G.J.","last_name":"Scheele","first_name":"Colinda L.G.J."},{"full_name":"Kishi, Kasumi","id":"3065DFC4-F248-11E8-B48F-1D18A9856A87","first_name":"Kasumi","last_name":"Kishi"},{"full_name":"Ellenbroek, Saskia I.J.","first_name":"Saskia I.J.","last_name":"Ellenbroek"},{"last_name":"Simons","first_name":"Benjamin D.","full_name":"Simons, Benjamin D."},{"last_name":"Van Rheenen","first_name":"Jacco","full_name":"Van Rheenen, Jacco"},{"last_name":"Hannezo","orcid":"0000-0001-6005-1561","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"}],"issue":"29","ddc":["570"],"acknowledgement":"We thank all members of the E.H., B.D.S., and J.v.R. groups for stimulating discussions. This project was supported by\r\nthe European Research Council (648804 to J.v.R. and 851288 to E.H.). It has also received support from the CancerGenomics.nl (Netherlands Organization for Scientific Research) program (J.v.R.) and the Doctor Josef Steiner Foundation (J.v.R). B.D.S. was supported by Royal Society E. P. Abraham Research Professorship RP/R1/180165 and Wellcome Trust Grant 098357/Z/12/Z.","article_type":"original","page":"16969-16975","doi":"10.1073/pnas.1921205117","has_accepted_license":"1","type":"journal_article"}