Impact of autophagy on lymphocyte stemness

Efficient T cell responses rely on heterogeneity, characterized by the rise of effector and memory cells. Autophagy, responsible for homeostatic degradation and recycling of cell cargo, is crucial for T cell differentiation. Upon ageing, autophagy is impaired, which is detrimental for the generation of memory cells retaining stemness.

Interestingly, I have observed that naïve CD8+ T cells from aged mice are unable to undergo asymmetric cell division (ACD) (unpublished). ACD is a conserved mechanism to generate diversity, by endowing daughter cells with different fate determinants.

As both autophagy and ACD are involved in T cell differentiation and impaired upon ageing, unravelling how they synergistically influence T cell stemness is at the centre of this project.

We propose to use state-of-the-art imaging, proteomics, and metabolomics to investigate whether autophagy impacts cell asymmetries upon T cell mitosis.

Functional validation will be addressed by using the novel combination of autophagy-deficient and organelle-tagged cells (SnapTag mice), which will enable us to evaluate whether asymmetry inheritance of cell cargoes leads to asymmetric fates in vivo.

We anticipate that this research will be relevant to better understand how stemness is coordinated, and potentially lead to the development of therapeutic strategies in the context of regenerative medicine.