Stress-induced exit from dormancy drives DNA damage and cellular attrition within the hematopoietic stem cell compartment
Status: This talk is in preparation - details may change
The gradual accumulation of DNA damage within somatic cells is thought to be a hallmark of aging and a key mechanism via which both age-associated tissue degeneration and malignant transformation are mediated. Within the hematopoietic system, DNA damage in the hematopoietic stem cell (HSC) compartment is likely to be of the most biological relevance to tissue aging, since HSCs are the ultimate source of all blood cells throughout the lifetime of an organism and the cumulative attrition of these cells would eventually cause hematopoietic collapse. Furthermore, the longevity of HSCs means that they would also potentially survive long enough to acquire the multiple independent driver mutations that would be required for malignant transformation. Currently, little is known about the physiologic source of DNA damage in HSCs in vivo during aging despite the fact that recent whole genome sequencing efforts indicate that elderly humans accumulate several hundred mutations per HSC genome. Work in the Milsom laboratory focuses on stress as a mediator of physiologic aging within the adult stem cell compartment. Recent work from the group has demonstrated that exposure of mice to agonists that mimic infection or acute blood loss can drive the acquisition of DNA damage in the HSC compartment in vivo, leading to HSC exhaustion and eventual bone marrow failure in the setting of a non-function Fanconi anemia DNA repair pathway (Walter et al., 2015, Nature).
Date: 26 March 2015, 11:00
Venue: MRC Weatherall Institute of Molecular Medicine, Headington OX3 9DS
Venue Details: Seminar Room
Speaker: Dr Michael Milsom (German Cancer Research Centre)
Organiser: Penny Berry (University of Oxford, Department of Oncology, Weatherall Institute of Molecular Medicine)
Organiser contact email address: penny.bery@oncology.ox.ac.uk
Host: Dr Wojciech Niedzwiedz (WIMM)
Topics:
Booking required?: Not required
Audience: Members of the University only
Editor: Penny Berry