Paris Postdoc seminar – Silvia Torchio

Invited by the Institut Jacques Monod, Silvia Torchio (Fate and plasticity of epithelial stem cells Lab, Developmental Biology and Genetics Unit (UMR3215/U934), Institut Curie) will present a Paris Postdoc Seminar on the theme:

The gut at a cROSsroad: how Reactive Oxygen Species shape cell fate decisions

Abstract:

Stem cells have to continuously balance between self-renewal and differentiation. Although we know a great deal about the genetic, epigenetic, and mechanical cues controlling stem cell fate decisions, the contribution of biochemical signaling such as Reactive Oxygen Species (ROS)-mediated is still poorly understood. We thus investigated redox as a potential mechanism governing stem cell fate decisions in the context of the murine small intestine, leveraging organoids as a model. We determined that ROS concentration is higher in stem cells than in differentiated lineages, both in vitro and ex vivo; this difference is crucial to maintain balanced cell type composition in organoids, as ROS alterations skew stem cell differentiation versus self-renewal equilibrium. Moreover, increasing ROS levels in differentiated Paneth cells triggers their reentry into the cell cycle, in a process akin to regeneration. Furthermore, we show that a ROS spike is crucial during development for the maturation of fetal progenitors into the adult stem cell pool. Collectively, our work shows that redox signaling acts as a conserved mechanism to regulate stem cell fate decisions in the mouse small intestine, both during development and in adult homeostasis.