Stemness within an Involuting Organ: Implications for Thymus Regeneration

Host

Carlos Minutti, Principal Investigator, Champalimaud Research

Venue

Seminar room

Abstract

The thymus is a primary lymphoid organ underpinning adaptive immunity that provides defence against pathogens, cancer and establishes long-term immune memory. However, the thymus starts involuting in early life and continues into adulthood with atrophy in the elderly and yet it maintains a regenerative capacity. Current models for thymic regeneration are based on inducing injury though the underpinning mechanisms are unknown. We have recently identified and characterized bona fide epithelial stem cells (SC) with multilineage differentiation potency in the post-natal thymus that are distinct from progenitors. Thymic SC are long-lived in humans and are defined by several unique cellular and molecular traits that are maintained in vitro where they self-renew and can be extensively expanded, akin to stem cells of constantly renewing tissues. These results were obtained thanks to a combination of single cell transcriptomic and proteomic analyses of thymic stroma, that also allowed the recognition of novel specialized populations. Finally, the identification of a distinctive molecular signature combined with spatial multi-omics of thymic SC allowed us to define the location and molecular features of their niches and design novel differentiation assays ex vivo. This offers a new perspective and conceptual advance to study the mechanisms of thymic involution and design new strategies for rejuvenating the adaptive immune system.

Biography

Paola Bonfanti is Group Leader at the Francis Crick Institute and Professor of Epithelial Cell Biology & Regenerative Medicine at UCL. Paola received her MD degree from the University of Milan and her PhD from the EPFL in Lausanne. She moved to the VUB in Brussels for her postdoctoral training with a Long-Term EMBO fellowship and a Young Investigator Award from the EFSD/JDRF/Roche. She established her laboratory in 2014 thanks to the award of a UCL Excellence Fellowship and an ERC StG.
 

Register here.
 

About CR Colloquia Series

Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.