PUBLICATION
Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics
- Authors
- Unterweger, I.A., Klepstad, J., Hannezo, E., Lundegaard, P.R., Trusina, A., Ober, E.A.
- ID
- ZDB-PUB-231005-59
- Date
- 2023
- Source
- PLoS Biology 21: e3002315e3002315 (Journal)
- Registered Authors
- Lundegaard, Pia Rengtved, Ober, Elke
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cell Lineage
- Cell Proliferation
- Epithelial Cells
- Hepatocytes/metabolism
- Liver*/metabolism
- Zebrafish*
- PubMed
- 37792696 Full text @ PLoS Biol.
Citation
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:e3002315e3002315.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping