Research Focus

The aim of my group is to understand how progenitor cells of the pancreas read architectural cues to choose between expansion and differentiation. We use these principles to recapitulate the process in vitro from stem cells.

Organoid models of pancreas development and diabetes

We have developed 3D models of pancreas development in a dish (pancreas organoids) starting from mouse embryo cells, or engineered from human pluripotent stem cells (ESCs, iPSCs). We notably established a single cell transcriptome atlas of the cells in organoids and benchmarked this to the fetal human pancreas. Using genetic modifications of human stem cells we use human organoids to study how genes expressed during pregnancy predispose the fetus to subsequent development of diabetes.

Engineering beta cells in vitro from stem cells

We produce pancreas progenitors from stem cells and have established protocols to expand them. These cells can be further differentiated into beta cells. This enables to upscale the process of beta cell production with the ultimate aim of a therapeutic transplantation for diabetes therapy.

Contributions of individual cells to an organ community

Using human and mouse organoids, 2D stem cell cultures, mouse genetics and live imaging, we study how each cell makes decisions to proliferate or differentiate. We investigate how architectural cues deployed along ducts control the differentiation of endocrine cells, notably the links between planar cell polarity, ductal flow and cilia. By understanding the process we hope to control it and generate numerous beta cells for diabetes therapy.

Future Projects and Goals

• Understand what promotes the maturation and functionality of b-cells
• Use directed differentiation of human pluripotent stem cells into beta cells to understand human endocrine development and develop cell therapies for diabetes
• Develop models enabling to understand how mutations affecting development predispose to diabetes later in life
• Use organoids for screens aiming at identifying pathways controlling pancreas and endocrine cell differentiation and morphogenesis