Multilineage communication regulates human liver bud development from pluripotency

Posted on Posted in AMRC Research

Date: 14 Jun 2017

 

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues1; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing2,3 to reconstruct hepatocyte-like lineage progression from pluripotency in twodimensional culture. We then derive three-dimensional liver bud organoids4 by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during liver bud development. We find that liver bud hepatoblasts diverge from the two-dimensional lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark three dimensional liver buds against fetal and adult human liver single cell RNA sequencing data, and find a striking correspondence between the three-dimensional liver bud and fetal liver cells. We use a receptor–ligand pairing analysis and a high-throughput inhibitor assay to interrogate signalling in liver buds, and show that vascular endothelial growth factor (VEGF) crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development.

 

Link to full article on Nature

Link to press release

Pennisi, E. (2017). Mini-livers reveal fine details of organ development. Science, [online] (6343), p.1109.

For inquiries regarding this press release

Keisuke SEKINE

E-mail: ksekine@yokohama-cu.ac.jp   Phone: +81 45 787 2688

 

Takanori TAKEBE

E-mail: ttakebe@yokohama-cu.ac.jp   Phone: +81 45 787 2672

 

Hideki TANIGUCHI

E-mail: rtanigu@yokohama-cu.ac.jp   Phone: +81 45 787 8963

Department of Regenerative Medicine,
Yokohama City University School of Medicine

Fukuura 3-9, Kanazawa-ku, Yokohama, Japan 236-0004