--- _id: '10825' abstract: - lang: eng 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. 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. article_processing_charge: No article_type: original author: - first_name: Ayaka full_name: Yanagida, Ayaka last_name: Yanagida - first_name: Elena full_name: Corujo-Simon, Elena last_name: Corujo-Simon - first_name: Christopher K. full_name: Revell, Christopher K. last_name: Revell - first_name: Preeti full_name: Sahu, Preeti id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E last_name: Sahu - first_name: Giuliano G. full_name: Stirparo, Giuliano G. last_name: Stirparo - first_name: Irene M. full_name: Aspalter, Irene M. last_name: Aspalter - first_name: Alex K. full_name: Winkel, Alex K. last_name: Winkel - first_name: Ruby full_name: Peters, Ruby last_name: Peters - first_name: Henry full_name: De Belly, Henry last_name: De Belly - first_name: Davide A.D. full_name: Cassani, Davide A.D. last_name: Cassani - first_name: Sarra full_name: Achouri, Sarra last_name: Achouri - first_name: Raphael full_name: Blumenfeld, Raphael last_name: Blumenfeld - first_name: Kristian full_name: Franze, Kristian last_name: Franze - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Ewa K. full_name: Paluch, Ewa K. last_name: Paluch - first_name: Jennifer full_name: Nichols, Jennifer last_name: Nichols - first_name: Kevin J. full_name: Chalut, Kevin J. last_name: Chalut citation: ama: Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate early embryonic lineage sorting. Cell. 2022;185(5):777-793.e20. doi:10.1016/j.cell.2022.01.022 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. Cell. Cell Press. https://doi.org/10.1016/j.cell.2022.01.022 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.” Cell. Cell Press, 2022. https://doi.org/10.1016/j.cell.2022.01.022. ieee: A. Yanagida et al., “Cell surface fluctuations regulate early embryonic lineage sorting,” Cell, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022. 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.” Cell, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20, doi:10.1016/j.cell.2022.01.022. 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. date_created: 2022-03-06T23:01:52Z date_published: 2022-02-22T00:00:00Z date_updated: 2023-08-02T14:43:50Z day: '22' ddc: - '570' department: - _id: EdHa doi: 10.1016/j.cell.2022.01.022 ec_funded: 1 external_id: isi: - '000796293700007' pmid: - '35196500' file: - access_level: open_access checksum: ae305060e8031297771b89dae9e36a29 content_type: application/pdf creator: dernst date_created: 2022-03-07T07:55:23Z date_updated: 2022-03-07T07:55:23Z file_id: '10831' file_name: 2022_Cell_Yanagida.pdf file_size: 8478995 relation: main_file success: 1 file_date_updated: 2022-03-07T07:55:23Z has_accepted_license: '1' intvolume: ' 185' isi: 1 issue: '5' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 777-793.e20 pmid: 1 project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: Cell publication_identifier: eissn: - '10974172' issn: - '00928674' publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: Cell surface fluctuations regulate early embryonic lineage sorting tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 185 year: '2022' ... --- _id: '10178' abstract: - lang: eng 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. 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" article_number: '093043' article_processing_charge: Yes article_type: original author: - first_name: Preeti full_name: Sahu, Preeti id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E last_name: Sahu - first_name: J. M. full_name: Schwarz, J. M. last_name: Schwarz - first_name: M. Lisa full_name: Manning, M. Lisa last_name: Manning citation: ama: Sahu P, Schwarz JM, Manning ML. Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. New Journal of Physics. 2021;23(9). doi:10.1088/1367-2630/ac23f1 apa: Sahu, P., Schwarz, J. M., & Manning, M. L. (2021). Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. New Journal of Physics. IOP Publishing. https://doi.org/10.1088/1367-2630/ac23f1 chicago: Sahu, Preeti, J. M. Schwarz, and M. Lisa Manning. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” New Journal of Physics. IOP Publishing, 2021. https://doi.org/10.1088/1367-2630/ac23f1. ieee: P. Sahu, J. M. Schwarz, and M. L. Manning, “Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue,” New Journal of Physics, vol. 23, no. 9. IOP Publishing, 2021. 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. mla: Sahu, Preeti, et al. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” New Journal of Physics, vol. 23, no. 9, 093043, IOP Publishing, 2021, doi:10.1088/1367-2630/ac23f1. short: P. Sahu, J.M. Schwarz, M.L. Manning, New Journal of Physics 23 (2021). date_created: 2021-10-24T22:01:34Z date_published: 2021-09-29T00:00:00Z date_updated: 2023-08-14T08:10:31Z day: '29' ddc: - '570' department: - _id: EdHa doi: 10.1088/1367-2630/ac23f1 external_id: arxiv: - '2102.05397' isi: - '000702042400001' file: - access_level: open_access checksum: ace603e8f0962b3ba55f23fa34f57764 content_type: application/pdf creator: cziletti date_created: 2021-10-28T12:06:01Z date_updated: 2021-10-28T12:06:01Z file_id: '10193' file_name: 2021_NewJPhys_Sahu.pdf file_size: 2215016 relation: main_file success: 1 file_date_updated: 2021-10-28T12:06:01Z has_accepted_license: '1' intvolume: ' 23' isi: 1 issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: New Journal of Physics publication_identifier: eissn: - '13672630' publication_status: published publisher: IOP Publishing quality_controlled: '1' scopus_import: '1' status: public title: Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 23 year: '2021' ...