Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics

Unterweger IA, Klepstad J, Hannezo E, Lundegaard PR, Trusina A, Ober EA (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Plos Biology Public Library of Science

Book Volume: 21

Article Number: e3002315

Journal Issue: 10

DOI: 10.1371/journal.pbio.3002315

Abstract

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.

Authors with CRIS profile

Elke Ober

Involved external institutions

University of Copenhagen DK Denmark (DK) Niels Bohr Institute / Niels Bohr Institutet DK Denmark (DK) Institute of Science and Technology Austria (IST Austria) AT Austria (AT)

How to cite

APA:

Unterweger, I.A., Klepstad, J., Hannezo, E., 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, 21(10). https://dx.doi.org/10.1371/journal.pbio.3002315

MLA:

Unterweger, Iris A., et al. "Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics." Plos Biology 21.10 (2023).

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