Conférence - Emmanuelle Passegué : Hematopoietic Stem Cell Aging and Adaptation to Stress

Hugues de ThéCollège de FranceOncologie cellulaire et moléculaireAnnée 2025-2026Hematopoietic Stem Cell Aging and Adaptation to StressConférence - Emmanuelle Passegué : Adaptive and Maladaptive Myeloid Cell ProductionEmmanuelle PasseguéDirectrice de la Columbia Stem Cell Initiative et professeure émérite de génétique et de développement à l'université ColumbiaRésuméAlthough young adult HSCs employ finely tuned mechanisms to balance pro-survival and stress responses, these maintenance strategies provoke vulnerabilities that manifest with continued age, leading to a decline in function. We will examine HSC biology through the lens of antagonistic pleiotropy, whereby the same mechanisms that are important for reproductive fitness form the basis for functional decline during aging. We will particularly highlight the central role of cell cycle regulation, niche cell reliance, inflammatory responses, cellular memory, and distinct metabolic regulation in driving HSC aging features, including expansion of the HSC pool, decreased self-renewal ability, myeloid-biased differentiation, and genomic instability leading to clonal hematopoiesis (CH) and leukemic transformation.