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Single-cell RNA-seq Analysis of Pancreatic and Hepatic Progenitor Cells from Tg(Prox1-EGFP) Transgenic Mouse Embryos

ABSTRACT: Formation of the hepato-pancreato-biliary organ system in mammals is a paradigm for organogenesis, whereby a small progenitor population of the ventral foregut gives rise to a multitude of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. The multipotent ventral foregut cell population undergoes an initial fate segregation into hepatic and pancreato-biliary progenitors in response to signaling cues from surrounding mesodermal tissues. Subsequently, pancreato-biliary progenitors give rise to ventral pancreatic and gallbladder progenitors. In this study, we used single-cell RNA sequencing to molecularly characterize progenitor populations in the ventral foregut that contribute to the formation of hepatic, pancreatic, and biliary organ rudiments throughout organogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE144103 | GEO | 2021/07/13

REPOSITORIES: GEO

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Project description:Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in stem cell biology. This knowledge will aid in the targeted differentiation and growth of stem cells, but also in the discovery of the basis of cellular plasticity and of how tissue programming can be controlled. The liver and pancreas share many aspects of their early development, being both specified in the same region of the endoderm, and, possibly, originating from a common progenitor. However, how pancreas versus liver cell fate decision occurs during embryogenesis and the molecular basis of this cellular plasticity are poorly understood. Here, we use RNA-Seq to define the molecular identity of liver and pancreas progenitors directly in mouse embryos and to investigate the mechanisms regulating the emergence of liver or pancreas as alternative fates from the endoderm. Progenitor cell-specific RNA was obtained from mouse Prox1-EGFP-labeled embryonic cells isolated by FACS at distinct developmental stages, before and after the onset of organogenesis. By integrating the temporal and spatial gene expression profiles, we found mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the non-canonical Wnt pathway as a potential developmental regulator of the pancreas versus liver fate decision, being expressed in the foregut endoderm, before the cell fate choice is made, and then maintained in pancreas progenitors but absent in hepatic progenitors. Moreover, when assayed in Xenopus embryos, the non-canonical Wnt pathway is able to promote pancreatic fate and repress hepatic fate in the endoderm, suggesting an ancient mechanism for controlling pancreas versus liver fate choice. We expect that this knowledge will be key to formulate reprogramming strategies to convert adult hepatic cells into pancreatic cells as a cell-based therapeutic approach for diabetes. We performed sequencing-based expression profiling (RNA-Seq) of hepatic and pancreatic progenitors in the mouse at two distinct developmental stages.

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Single-cell RNA-seq Analysis of Pancreatic and Hepatic Progenitor Cells from Tg(Prox1-EGFP) Transgenic Mouse Embryos

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