[{"department":[{"_id":"EdHa"}],"date_updated":"2026-05-20T08:52:01Z","year":"2025","_id":"20424","quality_controlled":"1","abstract":[{"lang":"eng","text":"Homeostasis relies on a precise balance of fate choices between renewal and differentiation. Although progress has been done to characterize the dynamics of single-cell fate choices, their underlying mechanistic basis often remains unclear. Concentrating on skin epidermis as a paradigm for multilayered tissues with complex fate choices, we develop a 3D vertex-based model with proliferation in the basal layer, showing that mechanical competition for space naturally gives rise to homeostasis and neutral drift dynamics that are seen experimentally. We then explore the effect of introducing mechanical heterogeneities between cellular subpopulations. We uncover that relatively small tension heterogeneities, reflected by distinct morphological changes in single-cell shapes, can be sufficient to heavily tilt cellular dynamics towards exponential growth. We thus derive a master relationship between cell shape and long-term clonal dynamics, which we validated during basal cell carcinoma initiation in mouse epidermis. Altogether, we propose a theoretical framework to link mechanical forces, quantitative cellular morphologies and cellular fate outcomes in complex tissues."}],"acknowledgement":"We thank Alois Schlögl, Paula Sanematsu, Susana Moreno Flores, Bernat Corominas-Murtra, Stefania Tavano, Gayathri Singharaju, and Hannezo group members for helpful discussions, the Bioimaging facility at ISTA, as well as Matthias Merkel and Lisa Manning for sharing the 3D Voronoi code. We also thank the Champalimaud animal facility, Anna Pezzarossa and the Champalimaud ABBE platform for the help with microscopy and image processing. This work was supported by EMBO (ALTF 522-2021), a Fundação para a Ciência e Tecnologia grant to A.S.D. (PTDC/MED-ONC/5553/2020), as well as the European Research Council (grant 851288 to EH). A.S.D., S.C., and R.M.S. are supported by QuantOCancer Project Horizon European Union’s Horizon 2020 program (grant agreement No 810653).","date_created":"2025-10-05T22:01:34Z","isi":1,"article_type":"original","article_number":"8440","pmid":1,"OA_place":"publisher","day":"26","oa_version":"Published Version","oa":1,"publication_identifier":{"eissn":["2041-1723"]},"OA_type":"gold","citation":{"chicago":"Sahu, Preeti, Sara Monteiro-Ferreira, Sara Canato, Raquel Maia Soares, Adriana Sánchez-Danés, and Edouard B Hannezo. “Mechanical Control of Cell Fate Decisions in the Skin Epidermis.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-62882-9\">https://doi.org/10.1038/s41467-025-62882-9</a>.","ieee":"P. Sahu, S. Monteiro-Ferreira, S. Canato, R. M. Soares, A. Sánchez-Danés, and E. B. Hannezo, “Mechanical control of cell fate decisions in the skin epidermis,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","short":"P. Sahu, S. Monteiro-Ferreira, S. Canato, R.M. Soares, A. Sánchez-Danés, E.B. Hannezo, Nature Communications 16 (2025).","apa":"Sahu, P., Monteiro-Ferreira, S., Canato, S., Soares, R. M., Sánchez-Danés, A., &#38; Hannezo, E. B. (2025). Mechanical control of cell fate decisions in the skin epidermis. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-62882-9\">https://doi.org/10.1038/s41467-025-62882-9</a>","ista":"Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo EB. 2025. Mechanical control of cell fate decisions in the skin epidermis. Nature Communications. 16, 8440.","ama":"Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo EB. Mechanical control of cell fate decisions in the skin epidermis. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-62882-9\">10.1038/s41467-025-62882-9</a>","mla":"Sahu, Preeti, et al. “Mechanical Control of Cell Fate Decisions in the Skin Epidermis.” <i>Nature Communications</i>, vol. 16, 8440, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-62882-9\">10.1038/s41467-025-62882-9</a>."},"article_processing_charge":"Yes","title":"Mechanical control of cell fate decisions in the skin epidermis","date_published":"2025-09-26T00:00:00Z","publisher":"Springer Nature","author":[{"last_name":"Sahu","full_name":"Sahu, Preeti","first_name":"Preeti","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E"},{"full_name":"Monteiro-Ferreira, Sara","first_name":"Sara","last_name":"Monteiro-Ferreira"},{"last_name":"Canato","full_name":"Canato, Sara","first_name":"Sara"},{"last_name":"Soares","full_name":"Soares, Raquel Maia","first_name":"Raquel Maia"},{"first_name":"Adriana","full_name":"Sánchez-Danés, Adriana","last_name":"Sánchez-Danés"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","last_name":"Hannezo","full_name":"Hannezo, Edouard B","first_name":"Edouard B"}],"ec_funded":1,"language":[{"iso":"eng"}],"APC_amount":"7068 EUR","volume":16,"ddc":["570"],"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"publication_status":"published","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","status":"public","acknowledged_ssus":[{"_id":"Bio"}],"intvolume":"        16","file":[{"date_created":"2025-10-13T12:37:04Z","creator":"dernst","access_level":"open_access","file_id":"20464","file_name":"2025_NatureComm_Sahu.pdf","date_updated":"2025-10-13T12:37:04Z","file_size":2816813,"content_type":"application/pdf","success":1,"relation":"main_file","checksum":"d1656576883b23902545328e2d640234"}],"file_date_updated":"2025-10-13T12:37:04Z","external_id":{"pmid":["41006218"],"isi":["001582555200011"]},"doi":"10.1038/s41467-025-62882-9","publication":"Nature Communications","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","project":[{"_id":"628f3fb1-2b32-11ec-9570-83ce778803f7","name":"Biomechanics of stem cell fate determination","grant_number":"ALTF 522-2021"},{"name":"Design Principles of Branching Morphogenesis","grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020"}],"has_accepted_license":"1","month":"09","type":"journal_article","DOAJ_listed":"1"},{"citation":{"ieee":"A. Yanagida <i>et al.</i>, “Cell surface fluctuations regulate early embryonic lineage sorting,” <i>Cell</i>, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022.","chicago":"Yanagida, Ayaka, Elena Corujo-Simon, Christopher K. Revell, Preeti Sahu, Giuliano G. Stirparo, Irene M. Aspalter, Alex K. Winkel, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>. Cell Press, 2022. <a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">https://doi.org/10.1016/j.cell.2022.01.022</a>.","apa":"Yanagida, A., Corujo-Simon, E., Revell, C. K., Sahu, P., Stirparo, G. G., Aspalter, I. M., … Chalut, K. J. (2022). Cell surface fluctuations regulate early embryonic lineage sorting. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">https://doi.org/10.1016/j.cell.2022.01.022</a>","short":"A. Yanagida, E. Corujo-Simon, C.K. Revell, P. Sahu, G.G. Stirparo, I.M. Aspalter, A.K. Winkel, R. Peters, H. De Belly, D.A.D. Cassani, S. Achouri, R. Blumenfeld, K. Franze, E.B. Hannezo, E.K. Paluch, J. Nichols, K.J. Chalut, Cell 185 (2022) 777–793.e20.","ama":"Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate early embryonic lineage sorting. <i>Cell</i>. 2022;185(5):777-793.e20. doi:<a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">10.1016/j.cell.2022.01.022</a>","ista":"Yanagida A, Corujo-Simon E, Revell CK, Sahu P, Stirparo GG, Aspalter IM, Winkel AK, Peters R, De Belly H, Cassani DAD, Achouri S, Blumenfeld R, Franze K, Hannezo EB, Paluch EK, Nichols J, Chalut KJ. 2022. Cell surface fluctuations regulate early embryonic lineage sorting. Cell. 185(5), 777–793.e20.","mla":"Yanagida, Ayaka, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20, doi:<a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">10.1016/j.cell.2022.01.022</a>."},"article_processing_charge":"No","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"oa":1,"pmid":1,"day":"22","oa_version":"Published Version","article_type":"original","isi":1,"date_created":"2022-03-06T23:01:52Z","_id":"10825","abstract":[{"text":"In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages.","lang":"eng"}],"acknowledgement":"We are grateful to H. Niwa for Dox regulatable PB vector; G. Charras for EzrinT567D cDNA; K. Jones for tdTomato ESCs, R26-Confetti ESCs, and laboratory assistance; M. Kinoshita for pPB-CAG-H2B-BFP plasmid; P. Humphreys and D. Clements for imaging support; G. Chu, P. Attlesey, and staff for animal husbandry; S. Pallett for laboratory assistance; C. Mulas for critical feedback on the project; T. Boroviak for single-cell RNA-seq; the EMBL Genomics Core Facility for sequencing; and M. Merkel for developing and sharing the original version of the 3D Voronoi code. This work was financially supported by BBSRC ( BB/Moo4023/1 and BB/T007044/1 to K.J.C. and J.N., Alert16 grant BB/R000042 to E.K.P.), Leverhulme Trust ( RPG-2014-080 to K.J.C. and J.N.), European Research Council ( 772798 -CellFateTech to K.J.C., 311637 -MorphoCorDiv and 820188 -NanoMechShape to E.K.P., Starting Grant 851288 to E.H., and 772426 -MeChemGui to K.F.), the Isaac Newton Trust (to E.K.P.), Medical Research Council UK (MRC program award MC_UU_00012/5 to E.K.P.), the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 641639 ( ITN Biopol , H.D.B. and E.K.P.), the Alexander von Humboldt Foundation (Alexander von Humboldt Professorship to K.F.), EMBO ALTF 522-2021 (to P.S.), Centre for Trophoblast Research (Next Generation fellowship to S.A.), and JSPS Overseas Research Fellowships (to A.Y.). The Wellcome-MRC Cambridge Stem Cell Institute receives core funding from Wellcome Trust ( 203151/Z/16/Z ) and MRC ( MC_PC_17230 ). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","quality_controlled":"1","year":"2022","department":[{"_id":"EdHa"}],"date_updated":"2025-07-10T11:50:00Z","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"02","has_accepted_license":"1","scopus_import":"1","issue":"5","project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288"}],"external_id":{"pmid":["35196500"],"isi":["000796293700007"]},"doi":"10.1016/j.cell.2022.01.022","file_date_updated":"2022-03-07T07:55:23Z","publication":"Cell","file":[{"file_id":"10831","access_level":"open_access","file_size":8478995,"date_updated":"2022-03-07T07:55:23Z","file_name":"2022_Cell_Yanagida.pdf","relation":"main_file","success":1,"content_type":"application/pdf","checksum":"ae305060e8031297771b89dae9e36a29","date_created":"2022-03-07T07:55:23Z","creator":"dernst"}],"license":"https://creativecommons.org/licenses/by/4.0/","intvolume":"       185","status":"public","page":"777-793.e20","ddc":["570"],"volume":185,"publication_status":"published","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"language":[{"iso":"eng"}],"title":"Cell surface fluctuations regulate early embryonic lineage sorting","author":[{"first_name":"Ayaka","full_name":"Yanagida, Ayaka","last_name":"Yanagida"},{"first_name":"Elena","full_name":"Corujo-Simon, Elena","last_name":"Corujo-Simon"},{"last_name":"Revell","full_name":"Revell, Christopher K.","first_name":"Christopher K."},{"full_name":"Sahu, Preeti","first_name":"Preeti","last_name":"Sahu","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E"},{"last_name":"Stirparo","first_name":"Giuliano G.","full_name":"Stirparo, Giuliano G."},{"first_name":"Irene M.","full_name":"Aspalter, Irene M.","last_name":"Aspalter"},{"first_name":"Alex K.","full_name":"Winkel, Alex K.","last_name":"Winkel"},{"last_name":"Peters","first_name":"Ruby","full_name":"Peters, Ruby"},{"last_name":"De Belly","full_name":"De Belly, Henry","first_name":"Henry"},{"first_name":"Davide A.D.","full_name":"Cassani, Davide A.D.","last_name":"Cassani"},{"full_name":"Achouri, Sarra","first_name":"Sarra","last_name":"Achouri"},{"last_name":"Blumenfeld","first_name":"Raphael","full_name":"Blumenfeld, Raphael"},{"full_name":"Franze, Kristian","first_name":"Kristian","last_name":"Franze"},{"last_name":"Hannezo","full_name":"Hannezo, Edouard B","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"last_name":"Paluch","first_name":"Ewa K.","full_name":"Paluch, Ewa K."},{"full_name":"Nichols, Jennifer","first_name":"Jennifer","last_name":"Nichols"},{"last_name":"Chalut","full_name":"Chalut, Kevin J.","first_name":"Kevin J."}],"ec_funded":1,"publisher":"Cell Press","date_published":"2022-02-22T00:00:00Z"},{"article_number":"093043","isi":1,"article_type":"original","arxiv":1,"date_created":"2021-10-24T22:01:34Z","quality_controlled":"1","acknowledgement":"We thank Paula Sanematsu, Matthias Merkel, Daniel Sussman, Cristina Marchetti and Edouard Hannezo for helpful discussions, and M Merkel for developing and sharing the original version of the 3D Voronoi code. This work was primarily funded by NSF-PHY-1607416, NSF-PHY-2014192 , and are in the division of physics at the National Science Foundation. PS and MLM acknowledge additional support from Simons Grant No. 454947.\r\n","abstract":[{"text":"In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features.","lang":"eng"}],"_id":"10178","department":[{"_id":"EdHa"}],"date_updated":"2026-04-02T13:54:56Z","year":"2021","article_processing_charge":"Yes","citation":{"ista":"Sahu P, Schwarz JM, Manning ML. 2021. Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. New Journal of Physics. 23(9), 093043.","ama":"Sahu P, Schwarz JM, Manning ML. Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. <i>New Journal of Physics</i>. 2021;23(9). doi:<a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">10.1088/1367-2630/ac23f1</a>","mla":"Sahu, Preeti, et al. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” <i>New Journal of Physics</i>, vol. 23, no. 9, 093043, IOP Publishing, 2021, doi:<a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">10.1088/1367-2630/ac23f1</a>.","chicago":"Sahu, Preeti, J. M. Schwarz, and M. Lisa Manning. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” <i>New Journal of Physics</i>. IOP Publishing, 2021. <a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">https://doi.org/10.1088/1367-2630/ac23f1</a>.","ieee":"P. Sahu, J. M. Schwarz, and M. L. Manning, “Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue,” <i>New Journal of Physics</i>, vol. 23, no. 9. IOP Publishing, 2021.","short":"P. Sahu, J.M. Schwarz, M.L. Manning, New Journal of Physics 23 (2021).","apa":"Sahu, P., Schwarz, J. M., &#38; Manning, M. L. (2021). Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. <i>New Journal of Physics</i>. IOP Publishing. <a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">https://doi.org/10.1088/1367-2630/ac23f1</a>"},"publication_identifier":{"eissn":["1367-2630"]},"oa":1,"day":"29","oa_version":"Published Version","status":"public","intvolume":"        23","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication_status":"published","ddc":["570"],"volume":23,"language":[{"iso":"eng"}],"date_published":"2021-09-29T00:00:00Z","publisher":"IOP Publishing","author":[{"full_name":"Sahu, Preeti","first_name":"Preeti","last_name":"Sahu","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E"},{"full_name":"Schwarz, J. M.","first_name":"J. M.","last_name":"Schwarz"},{"full_name":"Manning, M. Lisa","first_name":"M. Lisa","last_name":"Manning"}],"title":"Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue","type":"journal_article","issue":"9","scopus_import":"1","has_accepted_license":"1","month":"09","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication":"New Journal of Physics","file_date_updated":"2021-10-28T12:06:01Z","external_id":{"isi":["000702042400001"],"arxiv":["2102.05397"]},"doi":"10.1088/1367-2630/ac23f1","file":[{"content_type":"application/pdf","success":1,"relation":"main_file","checksum":"ace603e8f0962b3ba55f23fa34f57764","access_level":"open_access","file_id":"10193","file_name":"2021_NewJPhys_Sahu.pdf","file_size":2215016,"date_updated":"2021-10-28T12:06:01Z","creator":"cziletti","date_created":"2021-10-28T12:06:01Z"}]}]