Seminario - Biotecnologie e Bioscienze - Giovedì 13 marzo 2025, ore 16:30, edificio BIOS-U3, aula U3-04
Stefania Del Prete, German Cancer Research Center (DKFZ), Heidelberg, Germany
Abstract
The world is ageing, and investing in how to make elderly lives healthier is important. Elderly individuals are the most affected by the failure of the immune system associated with infectious diseases. Immune responses are sex-specific; women are less susceptible to infection but more often develop autoimmunity. Women and men differ in innate and adaptive immunity throughout life. This sex bias is not yet fully understood, but relies on a combination of hormonal and genetic factors, including the number of X chromosomes. In women, one X chromosome is inactivated to equalise the X-linked dosage between the sexes, but certain genes ‘escape’ X-inactivation and remain active. Since the X chromosome carries many immunity-related genes, their escape from X-inactivation and high dosage might affect the function of immune cells. However, which genes escape X-inactivation throughout life and what their impact on immune cell functions is, remains unclear. Using single-cell multiomics and F1 hybrid mice, the offspring of two evolutionary species whose genomes accumulated singlenucleotide variants, I performed allele-specific analysis to assess chromatin and transcriptional dynamics of immune cells across different age groups and sexes. My analysis revealed that age primarily dictates changes in cellular composition, while transcriptional changes are influenced by both sex and age. Additionally, I identified that escape genes exhibit cell type- and age-specific variations, leading to higher gene expression in females than in males, thereby shaping immunological trajectories.
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