Emmanuelle Passegué has been invited by the Collège de France assembly at the suggestion of Prs Hugues de Thé and Denis Duboule.
Hematopoiesis is a constant, vital function of the body by which all cells of the blood and immune system are produced throughout development, adulthood, and old age. Blood production by hematopoietic stem cells (HSC) supports oxygen transport, wound healing, and immunological responses during different stages of life, with dynamic regulations tailoring the production of particular lineages of blood cells through a complex array of intrinsic and extrinsic mechanisms. HSCs are equipped with a unique network of stress-response mechanisms that enable them to rapidly respond to organismal demand while simultaneously protecting themselves from insults. However, these pro-survival mechanisms provoke specific genetic, epigenetic, and metabolic forms of damage that accumulate over time, leading to an expanded pool of indolent and functionally degraded old HSCs. In this series of lectures, we will describe central features of HSC regulation during ontogeny to contextualize how adaptive responses over the life of the organism ultimately form the basis for HSC functional degradation with age. We will also discuss how the knowledge of age-related changes in HSC regulation can inform strategies for treating inflammatory disease conditions and rejuvenating old HSCs.
