{"publication_status":"published","quality_controlled":"1","date_updated":"2023-10-16T07:25:48Z","date_published":"2023-10-04T00:00:00Z","intvolume":"        21","publication_identifier":{"eissn":["1545-7885"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"related_material":{"link":[{"url":"https://github.com/JulieKlepstad/LiverDevelopment","relation":"software"}]},"author":[{"first_name":"Iris A.","last_name":"Unterweger","full_name":"Unterweger, Iris A."},{"last_name":"Klepstad","first_name":"Julie","full_name":"Klepstad, Julie"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Pia R.","last_name":"Lundegaard","full_name":"Lundegaard, Pia R."},{"last_name":"Trusina","first_name":"Ala","full_name":"Trusina, Ala"},{"full_name":"Ober, Elke A.","last_name":"Ober","first_name":"Elke A."}],"type":"journal_article","oa":1,"publisher":"Public Library of Science","doi":"10.1371/journal.pbio.3002315","file":[{"date_updated":"2023-10-16T07:20:49Z","date_created":"2023-10-16T07:20:49Z","file_size":6193110,"creator":"dernst","relation":"main_file","access_level":"open_access","checksum":"40a2b11b41d70a0e5939f8a52b66e389","file_id":"14431","success":1,"content_type":"application/pdf","file_name":"2023_PloSBiology_Unterweger.pdf"}],"file_date_updated":"2023-10-16T07:20:49Z","abstract":[{"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.","lang":"eng"}],"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).","date_created":"2023-10-15T22:01:10Z","language":[{"iso":"eng"}],"has_accepted_license":"1","day":"04","article_number":"e3002315","article_processing_charge":"No","_id":"14426","citation":{"apa":"Unterweger, I. A., Klepstad, J., Hannezo, E. B., Lundegaard, P. R., Trusina, A., &#38; Ober, E. A. (2023). Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002315\">https://doi.org/10.1371/journal.pbio.3002315</a>","mla":"Unterweger, Iris A., et al. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS Biology</i>, vol. 21, no. 10, e3002315, Public Library of Science, 2023, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002315\">10.1371/journal.pbio.3002315</a>.","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,” <i>PLoS Biology</i>, 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.","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. <i>PLoS Biology</i>. 2023;21(10). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002315\">10.1371/journal.pbio.3002315</a>","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.” <i>PLoS Biology</i>. Public Library of Science, 2023. <a href=\"https://doi.org/10.1371/journal.pbio.3002315\">https://doi.org/10.1371/journal.pbio.3002315</a>.","short":"I.A. Unterweger, J. Klepstad, E.B. Hannezo, P.R. Lundegaard, A. Trusina, E.A. Ober, PLoS Biology 21 (2023)."},"month":"10","issue":"10","department":[{"_id":"EdHa"}],"title":"Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","status":"public","ec_funded":1,"publication":"PLoS Biology","ddc":["570"],"volume":21,"project":[{"name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","grant_number":"851288"}],"article_type":"original","year":"2023","scopus_import":"1"}