--- _id: '14277' abstract: - lang: eng text: Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signaling pathways. Either feature alone can give rise to complex emergent phenomena, for example, mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological materials. We address this in Madin-Darby canine kidney (MDCK) monolayers, considering both mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from a uniform active glass to periodic spatiotemporal waves. We parametrize the model from published experimental data sets on MDCK monolayers and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves produce feedback on one another and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves at both the local and global levels. acknowledgement: We thank all members of the Hannezo group for discussions and suggestions, as well as Sound Wai Phow for technical assistance. This work received funding from the European Research Council under the EU Horizon 2020 research and innovation program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and the Ministry of Education under the Research Centres of Excellence program through the MBI at NUS. article_number: '013001' article_processing_charge: Yes article_type: original author: - first_name: Daniel R full_name: Boocock, Daniel R id: 453AF628-F248-11E8-B48F-1D18A9856A87 last_name: Boocock orcid: 0000-0002-1585-2631 - first_name: Tsuyoshi full_name: Hirashima, Tsuyoshi last_name: Hirashima - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 citation: ama: Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 2023;1(1). doi:10.1103/prxlife.1.013001 apa: Boocock, D. R., Hirashima, T., & Hannezo, E. B. (2023). Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. American Physical Society. https://doi.org/10.1103/prxlife.1.013001 chicago: Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” PRX Life. American Physical Society, 2023. https://doi.org/10.1103/prxlife.1.013001. ieee: D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers,” PRX Life, vol. 1, no. 1. American Physical Society, 2023. ista: Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001. mla: Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” PRX Life, vol. 1, no. 1, 013001, American Physical Society, 2023, doi:10.1103/prxlife.1.013001. short: D.R. Boocock, T. Hirashima, E.B. Hannezo, PRX Life 1 (2023). date_created: 2023-09-06T08:30:59Z date_published: 2023-07-20T00:00:00Z date_updated: 2023-09-15T06:39:17Z day: '20' ddc: - '570' department: - _id: EdHa doi: 10.1103/prxlife.1.013001 ec_funded: 1 file: - access_level: open_access checksum: f881d98c89eb9f1aa136d7b781511553 content_type: application/pdf creator: dernst date_created: 2023-09-15T06:30:50Z date_updated: 2023-09-15T06:30:50Z file_id: '14335' file_name: 2023_PRXLife_Boocock.pdf file_size: 2559520 relation: main_file success: 1 file_date_updated: 2023-09-15T06:30:50Z has_accepted_license: '1' intvolume: ' 1' issue: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: PRX Life publication_identifier: issn: - 2835-8279 publication_status: published publisher: American Physical Society quality_controlled: '1' status: public title: Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1 year: '2023' ... --- _id: '12710' abstract: - lang: eng text: Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, the interplay between the distribution of morphogens or micro-organisms and the emergence of curvature across length scales is addressed with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by-product of the chemical, biological, and mechanical processes but that curvature acts also as a signal that co-determines these processes. acknowledgement: B.S. and A.R. contributed equally to this work. A.P.G.C. and P.R.F. acknowledge the funding from Fundação para a Ciência e Tecnologia (Portugal), through IDMEC, under LAETA project UIDB/50022/2020. T.H.V.P. acknowledges the funding from Fundação para a Ciência e Tecnologia (Portugal), through Ph.D. Grant 2020.04417.BD. A.S. acknowledges that this work was partially supported by the ATTRACT Investigator Grant (no. A17/MS/11572821/MBRACE, to A.S.) from the Luxembourg National Research Fund. The author thanks Gerardo Ceada for his help in the graphical representations. N.A.K. acknowledges support from the European Research Council (grant 851960) and the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). M.B.A. acknowledges support from the French National Research Agency (grant ANR-201-8-CE1-3-0008 for the project “Epimorph”). G.E.S.T. acknowledges funding by the Australian Research Council through project DP200102593. A.C. acknowledges the funding from the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Grant CI 203/-2 1, the Spanish Ministry of Science and Innovation (PID2021-123013O-BI00) and the IKERBASQUE Basque Foundation for Science. article_number: '2206110' article_processing_charge: No article_type: review author: - first_name: Barbara full_name: Schamberger, Barbara last_name: Schamberger - first_name: Ricardo full_name: Ziege, Ricardo last_name: Ziege - first_name: Karine full_name: Anselme, Karine last_name: Anselme - first_name: Martine full_name: Ben Amar, Martine last_name: Ben Amar - first_name: Michał full_name: Bykowski, Michał last_name: Bykowski - first_name: André P.G. full_name: Castro, André P.G. last_name: Castro - first_name: Amaia full_name: Cipitria, Amaia last_name: Cipitria - first_name: Rhoslyn A. full_name: Coles, Rhoslyn A. last_name: Coles - first_name: Rumiana full_name: Dimova, Rumiana last_name: Dimova - first_name: Michaela full_name: Eder, Michaela last_name: Eder - first_name: Sebastian full_name: Ehrig, Sebastian last_name: Ehrig - first_name: Luis M. full_name: Escudero, Luis M. last_name: Escudero - first_name: Myfanwy E. full_name: Evans, Myfanwy E. last_name: Evans - first_name: Paulo R. full_name: Fernandes, Paulo R. last_name: Fernandes - first_name: Peter full_name: Fratzl, Peter last_name: Fratzl - first_name: Liesbet full_name: Geris, Liesbet last_name: Geris - first_name: Notburga full_name: Gierlinger, Notburga last_name: Gierlinger - 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: Aleš full_name: Iglič, Aleš last_name: Iglič - first_name: Jacob J.K. full_name: Kirkensgaard, Jacob J.K. last_name: Kirkensgaard - first_name: Philip full_name: Kollmannsberger, Philip last_name: Kollmannsberger - first_name: Łucja full_name: Kowalewska, Łucja last_name: Kowalewska - first_name: Nicholas A. full_name: Kurniawan, Nicholas A. last_name: Kurniawan - first_name: Ioannis full_name: Papantoniou, Ioannis last_name: Papantoniou - first_name: Laurent full_name: Pieuchot, Laurent last_name: Pieuchot - first_name: Tiago H.V. full_name: Pires, Tiago H.V. last_name: Pires - first_name: Lars D. full_name: Renner, Lars D. last_name: Renner - first_name: Andrew O. full_name: Sageman-Furnas, Andrew O. last_name: Sageman-Furnas - first_name: Gerd E. full_name: Schröder-Turk, Gerd E. last_name: Schröder-Turk - first_name: Anupam full_name: Sengupta, Anupam last_name: Sengupta - first_name: Vikas R. full_name: Sharma, Vikas R. last_name: Sharma - first_name: Antonio full_name: Tagua, Antonio last_name: Tagua - first_name: Caterina full_name: Tomba, Caterina last_name: Tomba - first_name: Xavier full_name: Trepat, Xavier last_name: Trepat - first_name: Sarah L. full_name: Waters, Sarah L. last_name: Waters - first_name: Edwina F. full_name: Yeo, Edwina F. last_name: Yeo - first_name: Andreas full_name: Roschger, Andreas last_name: Roschger - first_name: Cécile M. full_name: Bidan, Cécile M. last_name: Bidan - first_name: John W.C. full_name: Dunlop, John W.C. last_name: Dunlop citation: ama: 'Schamberger B, Ziege R, Anselme K, et al. Curvature in biological systems: Its quantification, emergence, and implications across the scales. Advanced Materials. 2023;35(13). doi:10.1002/adma.202206110' apa: 'Schamberger, B., Ziege, R., Anselme, K., Ben Amar, M., Bykowski, M., Castro, A. P. G., … Dunlop, J. W. C. (2023). Curvature in biological systems: Its quantification, emergence, and implications across the scales. Advanced Materials. Wiley. https://doi.org/10.1002/adma.202206110' chicago: 'Schamberger, Barbara, Ricardo Ziege, Karine Anselme, Martine Ben Amar, Michał Bykowski, André P.G. Castro, Amaia Cipitria, et al. “Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales.” Advanced Materials. Wiley, 2023. https://doi.org/10.1002/adma.202206110.' ieee: 'B. Schamberger et al., “Curvature in biological systems: Its quantification, emergence, and implications across the scales,” Advanced Materials, vol. 35, no. 13. Wiley, 2023.' ista: 'Schamberger B, Ziege R, Anselme K, Ben Amar M, Bykowski M, Castro APG, Cipitria A, Coles RA, Dimova R, Eder M, Ehrig S, Escudero LM, Evans ME, Fernandes PR, Fratzl P, Geris L, Gierlinger N, Hannezo EB, Iglič A, Kirkensgaard JJK, Kollmannsberger P, Kowalewska Ł, Kurniawan NA, Papantoniou I, Pieuchot L, Pires THV, Renner LD, Sageman-Furnas AO, Schröder-Turk GE, Sengupta A, Sharma VR, Tagua A, Tomba C, Trepat X, Waters SL, Yeo EF, Roschger A, Bidan CM, Dunlop JWC. 2023. Curvature in biological systems: Its quantification, emergence, and implications across the scales. Advanced Materials. 35(13), 2206110.' mla: 'Schamberger, Barbara, et al. “Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales.” Advanced Materials, vol. 35, no. 13, 2206110, Wiley, 2023, doi:10.1002/adma.202206110.' short: B. Schamberger, R. Ziege, K. Anselme, M. Ben Amar, M. Bykowski, A.P.G. Castro, A. Cipitria, R.A. Coles, R. Dimova, M. Eder, S. Ehrig, L.M. Escudero, M.E. Evans, P.R. Fernandes, P. Fratzl, L. Geris, N. Gierlinger, E.B. Hannezo, A. Iglič, J.J.K. Kirkensgaard, P. Kollmannsberger, Ł. Kowalewska, N.A. Kurniawan, I. Papantoniou, L. Pieuchot, T.H.V. Pires, L.D. Renner, A.O. Sageman-Furnas, G.E. Schröder-Turk, A. Sengupta, V.R. Sharma, A. Tagua, C. Tomba, X. Trepat, S.L. Waters, E.F. Yeo, A. Roschger, C.M. Bidan, J.W.C. Dunlop, Advanced Materials 35 (2023). date_created: 2023-03-05T23:01:06Z date_published: 2023-03-29T00:00:00Z date_updated: 2023-09-26T10:56:46Z day: '29' ddc: - '570' department: - _id: EdHa doi: 10.1002/adma.202206110 external_id: isi: - '000941068900001' pmid: - '36461812' file: - access_level: open_access checksum: 5c04d68130e97a0ecd1ca27fbc15a246 content_type: application/pdf creator: dernst date_created: 2023-09-26T10:51:56Z date_updated: 2023-09-26T10:51:56Z file_id: '14373' file_name: 2023_AdvancedMaterials_Schamberger.pdf file_size: 2898063 relation: main_file success: 1 file_date_updated: 2023-09-26T10:51:56Z has_accepted_license: '1' intvolume: ' 35' isi: 1 issue: '13' language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: Advanced Materials publication_identifier: eissn: - 1521-4095 issn: - 0935-9648 publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: 'Curvature in biological systems: Its quantification, emergence, and implications across the scales' 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 35 year: '2023' ... --- _id: '14279' abstract: - lang: eng text: "The zip file includes source data used in the manuscript \"CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration\", as well as a representative Jupyter notebook to reproduce the main figures. Please see the preprint on bioRxiv and the DOI link there to access the final published version. Note the title change between the preprint and the published manuscript.\r\nA sample script for particle-based simulations of collective chemotaxis by self-generated gradients is also included (see Self-generated_chemotaxis_sample_script.ipynb) to generate exemplary cell trajectories. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt." article_processing_charge: No author: - first_name: Mehmet C full_name: Ucar, Mehmet C id: 50B2A802-6007-11E9-A42B-EB23E6697425 last_name: Ucar orcid: 0000-0003-0506-4217 citation: ama: Ucar MC. Source data for the manuscript “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration.” 2023. doi:10.5281/ZENODO.8133960 apa: Ucar, M. C. (2023). Source data for the manuscript “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration.” Zenodo. https://doi.org/10.5281/ZENODO.8133960 chicago: Ucar, Mehmet C. “Source Data for the Manuscript ‘CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.’” Zenodo, 2023. https://doi.org/10.5281/ZENODO.8133960. ieee: M. C. Ucar, “Source data for the manuscript ‘CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration.’” Zenodo, 2023. ista: Ucar MC. 2023. Source data for the manuscript ‘CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration’, Zenodo, 10.5281/ZENODO.8133960. mla: Ucar, Mehmet C. Source Data for the Manuscript “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Zenodo, 2023, doi:10.5281/ZENODO.8133960. short: M.C. Ucar, (2023). date_created: 2023-09-06T08:39:25Z date_published: 2023-07-11T00:00:00Z date_updated: 2023-10-03T11:42:58Z day: '11' ddc: - '570' department: - _id: EdHa doi: 10.5281/ZENODO.8133960 has_accepted_license: '1' main_file_link: - open_access: '1' url: https://doi.org/10.5281/zenodo.8133960 month: '07' oa: 1 oa_version: Published Version publisher: Zenodo related_material: record: - id: '14274' relation: used_in_publication status: public status: public title: Source data for the manuscript "CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration" 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: research_data_reference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '12837' abstract: - lang: eng text: As developing tissues grow in size and undergo morphogenetic changes, their material properties may be altered. Such changes result from tension dynamics at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms controlling the physical state of growing tissues are unclear. We found that at early developmental stages, the epithelium in the developing mouse spinal cord maintains both high junctional tension and high fluidity. This is achieved via a mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the cell proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification uncovered here resembles a glass transition that depends on the dynamical stresses generated by proliferation and differentiation. Our finding that the fluidity of developing epithelia is linked to interkinetic nuclear movements and the dynamics of growth is likely to be relevant to multiple developing tissues. acknowledgement: 'We thank S. Hippenmeyer for the reagents and C. P. Heisenberg, J. Briscoe and K. Page for comments on the manuscript. This work was supported by IST Austria; the European Research Council under Horizon 2020 research and innovation programme grant no. 680037 and Horizon Europe grant 101044579 (A.K.); Austrian Science Fund (FWF): F78 (Stem Cell Modulation) (A.K.); ISTFELLOW postdoctoral program (A.S.); Narodowe Centrum Nauki, Poland SONATA, 2017/26/D/NZ2/00454 (M.Z.); and the Polish National Agency for Academic Exchange (M.Z.).' article_processing_charge: No article_type: original author: - first_name: Laura full_name: Bocanegra, Laura id: 4896F754-F248-11E8-B48F-1D18A9856A87 last_name: Bocanegra - first_name: Amrita full_name: Singh, Amrita id: 76250f9f-3a21-11eb-9a80-a6180a0d7958 last_name: Singh - 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: Marcin P full_name: Zagórski, Marcin P id: 343DA0DC-F248-11E8-B48F-1D18A9856A87 last_name: Zagórski orcid: 0000-0001-7896-7762 - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 citation: ama: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. 2023;19:1050-1058. doi:10.1038/s41567-023-01977-w apa: Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., & Kicheva, A. (2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-023-01977-w chicago: Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” Nature Physics. Springer Nature, 2023. https://doi.org/10.1038/s41567-023-01977-w. ieee: L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell cycle dynamics control fluidity of the developing mouse neuroepithelium,” Nature Physics, vol. 19. Springer Nature, pp. 1050–1058, 2023. ista: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. 2023. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. 19, 1050–1058. mla: Bocanegra, Laura, et al. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” Nature Physics, vol. 19, Springer Nature, 2023, pp. 1050–58, doi:10.1038/s41567-023-01977-w. short: L. Bocanegra, A. Singh, E.B. Hannezo, M.P. Zagórski, A. Kicheva, Nature Physics 19 (2023) 1050–1058. date_created: 2023-04-16T22:01:09Z date_published: 2023-07-01T00:00:00Z date_updated: 2023-10-04T11:14:05Z day: '01' ddc: - '570' department: - _id: EdHa - _id: AnKi doi: 10.1038/s41567-023-01977-w ec_funded: 1 external_id: isi: - '000964029300003' file: - access_level: open_access checksum: 858225a4205b74406e5045006cdd853f content_type: application/pdf creator: dernst date_created: 2023-10-04T11:13:28Z date_updated: 2023-10-04T11:13:28Z file_id: '14392' file_name: 2023_NaturePhysics_Boncanegra.pdf file_size: 5532285 relation: main_file success: 1 file_date_updated: 2023-10-04T11:13:28Z has_accepted_license: '1' intvolume: ' 19' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1050-1058 project: - _id: B6FC0238-B512-11E9-945C-1524E6697425 call_identifier: H2020 grant_number: '680037' name: Coordination of Patterning And Growth In the Spinal Cord - _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa grant_number: '101044579' name: Mechanisms of tissue size regulation in spinal cord development - _id: 059DF620-7A3F-11EA-A408-12923DDC885E grant_number: F07802 name: Morphogen control of growth and pattern in the spinal cord - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Nature Physics publication_identifier: eissn: - 1745-2481 issn: - 1745-2473 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '13081' relation: dissertation_contains status: public scopus_import: '1' status: public title: Cell cycle dynamics control fluidity of the developing mouse neuroepithelium 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 19 year: '2023' ... --- _id: '14426' abstract: - lang: eng text: To meet the physiological demands of the body, organs need to establish a functional tissue architecture and adequate size as the embryo develops to adulthood. In the liver, uni- and bipotent progenitor differentiation into hepatocytes and biliary epithelial cells (BECs), and their relative proportions, comprise the functional architecture. Yet, the contribution of individual liver progenitors at the organ level to both fates, and their specific proportion, is unresolved. Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is established (i) fast, (ii) solely by heterogeneous lineage decisions from uni- and bipotent progenitors, and (iii) independent of subsequent cell type–specific proliferation. Extending lineage tracing to adulthood determined that embryonic cells undergo spatially heterogeneous three-dimensional growth associated with distinct environments. Strikingly, giant clusters comprising almost half a ventral lobe suggest lobe-specific dominant-like growth behaviours. We show substantial hepatocyte polyploidy in juveniles representing another hallmark of postembryonic liver growth. Our findings uncover heterogeneous progenitor contributions to tissue architecture-defining cell type proportions and postembryonic organ growth as key mechanisms forming the adult liver. acknowledgement: "We thank the Ober group for discussion and comments on the manuscript. We are grateful to\r\nDr. F. Lemaigre for feedback on the manuscript and Dr. T. Piotrowski for invaluable support.\r\nWe thank the department of experimental medicine (AEM) in Copenhagen for expert fish\r\ncare. We gratefully acknowledge the DanStem Imaging Platform (University of Copenhagen)\r\nfor support and assistance in this work.\r\nThis work is supported by Novo Nordisk Foundation grant NNF17CC0027852 (EAO);\r\nNordisk Foundation grant NNF19OC0058327 (EAO); Novo Nordisk Foundation grant\r\nNNF17OC0031204 (PRL); https://novonordiskfonden.dk/en/; Danish National\r\nResearch Foundation grant DNRF116 (EAO and AT); https://dg.dk/en/; John and Birthe Meyer\r\nFoundation (PRL) and European Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme Grant Agreement No. 851288 (EH)." article_number: e3002315 article_processing_charge: No article_type: original author: - first_name: Iris A. full_name: Unterweger, Iris A. last_name: Unterweger - first_name: Julie full_name: Klepstad, Julie last_name: Klepstad - 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: Pia R. full_name: Lundegaard, Pia R. last_name: Lundegaard - first_name: Ala full_name: Trusina, Ala last_name: Trusina - first_name: Elke A. full_name: Ober, Elke A. last_name: Ober citation: ama: Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. PLoS Biology. 2023;21(10). doi:10.1371/journal.pbio.3002315 apa: Unterweger, I. A., Klepstad, J., Hannezo, E. B., Lundegaard, P. R., Trusina, A., & Ober, E. A. (2023). Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002315 chicago: Unterweger, Iris A., Julie Klepstad, Edouard B Hannezo, Pia R. Lundegaard, Ala Trusina, and Elke A. Ober. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” PLoS Biology. Public Library of Science, 2023. https://doi.org/10.1371/journal.pbio.3002315. ieee: I. A. Unterweger, J. Klepstad, E. B. Hannezo, P. R. Lundegaard, A. Trusina, and E. A. Ober, “Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics,” PLoS Biology, vol. 21, no. 10. Public Library of Science, 2023. ista: Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. 2023. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. PLoS Biology. 21(10), e3002315. mla: Unterweger, Iris A., et al. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” PLoS Biology, vol. 21, no. 10, e3002315, Public Library of Science, 2023, doi:10.1371/journal.pbio.3002315. short: I.A. Unterweger, J. Klepstad, E.B. Hannezo, P.R. Lundegaard, A. Trusina, E.A. Ober, PLoS Biology 21 (2023). date_created: 2023-10-15T22:01:10Z date_published: 2023-10-04T00:00:00Z date_updated: 2023-10-16T07:25:48Z day: '04' ddc: - '570' department: - _id: EdHa doi: 10.1371/journal.pbio.3002315 ec_funded: 1 file: - access_level: open_access checksum: 40a2b11b41d70a0e5939f8a52b66e389 content_type: application/pdf creator: dernst date_created: 2023-10-16T07:20:49Z date_updated: 2023-10-16T07:20:49Z file_id: '14431' file_name: 2023_PloSBiology_Unterweger.pdf file_size: 6193110 relation: main_file success: 1 file_date_updated: 2023-10-16T07:20:49Z has_accepted_license: '1' intvolume: ' 21' issue: '10' language: - iso: eng month: '10' oa: 1 oa_version: Published Version project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: PLoS Biology publication_identifier: eissn: - 1545-7885 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: link: - relation: software url: https://github.com/JulieKlepstad/LiverDevelopment scopus_import: '1' status: public title: Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 21 year: '2023' ...