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Multilineage communication regulates human liver bud development from pluripotency

MPG-Autoren
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Camp,  J. Gray
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Gerber,  Tobias
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Gac,  Malgorzata
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Kanton,  Sabina
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Kageyama,  Jorge
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Treutlein,  Barbara
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Zitation

Camp, J. G., Sekine, K., Gerber, T., Loeffler-Wirth, H., Binder, H., Gac, M., et al. (2017). Multilineage communication regulates human liver bud development from pluripotency. Nature, 546, 533-538. doi:10.1038/nature22796.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002D-72F0-5
Zusammenfassung
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.