IRB Barcelona BioMed Seminar
by Ana Martin-Villalba, PhD. – Division of Molecular Neurobiology – German Cancer Research Center (DKFZ) – Heidelberg – Germany
Stem cells show intrinsic interferon signalling, which protects them from viral infections. In the brain, type I interferon signalling increases in neural stem cells (NSCs) as they age and reduces their ability to become activated for repair. How interferon regulates stem cell activity and if it is coupled to an immune function remains poorly understood. To address this, we examined interferon receptor deficient mice and interferon-bexposed NSCs. At young ages, the activation rate of NSCs is strongly reduced in mutant mice and not further influenced by age. NSCs exposed to interferon-b arrested in G0 of the cell cycle and transiently increased their TOR signalling before also switching off this central signalling pathway to respond to external stimuli. Importantly, this regulation of TOR is needed to repress translation of key stem cell activity factors like Sox2. Single cell transcriptomes of the stem cell niche reveal that the increase of interferon signalling with age involves interferon receptors.While this is shared by endothelial cells and mature neurons, differentiating progeny remain unaffected by age. Our results show that interferons are key regulators of adult stem cell dynamics, beneficial in the young and harmful in the old brain.
Host: Manuel Serrano, PhD – Aging and Metabolism Programme – IRB Barcelona