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Home  > Press Release  > Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary

Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary

Takanori TAKEBE, Professor, Institute of Research, Division of Advanced Research

Abstract

Organogenesis is a complex and interconnected process that is orchestrated by multiple boundary tissue interactions1,2,3,4,5,6,7. However, it remains unclear how individual, neighbouring components coordinate to establish an integral multi-organ structure. Here we report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enables retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut–midgut boundary organoids in the absence of extrinsic factors. Whereas transplant-derived tissues are dominated by midgut derivatives, long-term-cultured microdissected hepato-biliary-pancreatic organoids develop into segregated multi-organ anlages, which then recapitulate early morphogenetic events including the invagination and branching of three different and interconnected organ structures, reminiscent of tissues derived from mouse explanted foregut–midgut culture. Mis-segregation of multi-organ domains caused by a genetic mutation in HES1 abolishes the biliary specification potential in culture, as seen in vivo8,9. In sum, we demonstrate that the experimental multi-organ integrated model can be established by the juxtapositioning of foregut and midgut tissues, and potentially serves as a tractable, manipulatable and easily accessible model for the study of complex human endoderm organogenesis.

Journal Article

JOURNAL:Nature

TITLE:Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary

DOI:https://doi.org/10.1038/s41586-019-1598-0

Correspondence to

Takanori TAKEBE, Professor
Organ and Tissue Neogenesis Consortium,
Advanced Multidisciplinary Research Cluster, Institute of Research
Tokyo Medical and Dental University(TMDU)
E-mail:ttakebe.ior(at)tmd.ac.jp


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