During embryonic development, the pancreas, gallbladder, and liver develop from a common pool of progenitors. Here, former BIH translational PhD student David Willnow from the Research group of Prof. Francesca Spagnoli and colleagues show that the development of these organs is not as separate as previously thought and identify a subpopulation of pancreatic progenitors that contribute cells to the rapidly growing liver. They suggest that this subpopulation, which sits at the border between the pancreato-biliary bud and the liver, is maintained in a multipotent state by signals coming from the adjacent intestine. Together, this work expands our understanding of the cellular processes driving early organogenesis.
Since many years, the group of Prof. Spagnoli is interested in elucidating the mechanisms at the origin of the two organs, liver and pancreas. The questions they study are: How distinct cell types, such as liver and pancreas, arise from common progenitors and acquire specialized shape to form functional organs? How plastic are these cellular states? Can cell plasticity between liver and pancreas be harnessed towards novel regenerative therapies for diabetes? Ultimately, the long-term goal is to translate these concepts into a treatment option for diabetes.
The work currently published in Nature expands current understanding of the cellular processes driving early organogenesis. These findings indicate sustained plasticity of the progenitor cells underlying hepato-pancreato-biliary development. Maintaining multipotent cells in a developing organ may have a similar purpose as maintaining a stem cell niche in an adult tissue. In this way, they provide homeostatic regulation and improve resilience during organogenesis—for example, following developmental delay or loss of a lineage-restricted cell population. Failure to maintain such a multipotent progenitor domain might result in human genetic syndromes as well as human malformations, featuring multi-organ phenotypes in liver, pancreas and gall bladder.
In order to show that multipotent progenitor cells that have the potential to populate the hepato-pancreato-biliary lineage tree persist in development David Willnow and the Spagnoli lab combined computational modelling and mouse genetics approaches. The next step is to study such plastic multipotent population in humans and exploit their potential for regenerative medicine. This might also help to elucidate the mechanisms underlying human genetic syndromes as well as human malformations, featuring multi-organ phenotypes in liver, pancreas and gall bladder.
Original Paper: David Willnow, Uwe Benary, Anca Margineanu, Maria Lillina Vignola, Fabian Konrath, Igor M Pongrac, Zahra Karimaddini, Alessandra Vigilante, Jana Wolf and Francesca M Spagnoli. Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche. Nature, DOI: doi.org/10.1038/s41586-021-03844-1