Professor Ludovic Vallier

Human pluripotent stem cells, control of differentiation and disease modeling

Understanding the mechanisms controlling early cell fate decisions in human development has major importance for regenerative medicine. Indeed the generation of fully functional cell types from stem cells is only achievable by recapitulating a normal succession of cell fate choice. The first event of differentiation of the embryo proper occurs at the stage of gastrulation with the specification of the three primary germ layers ectoderm, mesoderm and endoderm, from which all the cells of adult tissues are derived.

The main objective of our group is to define the molecular mechanisms controlling the transition between pluripotency and the endoderm lineage. For that, we use human pluripotent stem cells (hESCs and hIPSCs) as in vitro model of development to study the interplays between transcriptional networks, epigenetic modifications and cell cycle which ultimately orchestrate the earliest step of differentiation. The resulting knowledge allows the development of new culture system to drive differentiation of pluripotent stem cells into pancreatic, hepatic, lung and gut cells. These cells are then used to model disease in vitro and we have a specific focus on metabolic disorders affecting the liver and the pancreas. Furthermore, we are currently investigating how similar mechanisms could regulate adult stem cells self-renewal /differentiation during organ regeneration.

Overall, our objective is to uncover the common mechanisms controlling self-renewal and differentiation in both pluripotent and somatic stem cells.