Multilineage communication regulates human liver bud development from pluripotency.

Abstract:

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture. We then derive three-dimensional liver bud organoids 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.

PubMed ID: 28614297

Projects: Leipzig Melanoma Studies

Publication type: Not specified

Journal: Nature

Human Diseases: Liver disease

Citation: Nature. 2017 Jun 22;546(7659):533-538. doi: 10.1038/nature22796. Epub 2017 Jun 14.

Date Published: 22nd Jun 2017

Registered Mode: by PubMed ID

Authors: J. G. Camp, K. Sekine, T. Gerber, H. Loeffler-Wirth, H. Binder, M. Gac, S. Kanton, J. Kageyama, G. Damm, D. Seehofer, L. Belicova, M. Bickle, R. Barsacchi, R. Okuda, E. Yoshizawa, M. Kimura, H. Ayabe, H. Taniguchi, T. Takebe, B. Treutlein

Help
Activity

Views: 3206

Created: 6th May 2019 at 13:20

Last updated: 7th Dec 2021 at 17:58

help Attributions

None

Related items

Powered by
(v.1.13.0-master)
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies