Towards a quantitative understanding of somatic evolution in blood: missing drivers, ageing and other puzzles
This is a hybrid event - with the speaker attending in-person and viewable on Teams.
Somatic mutations acquired in healthy haematopoietic stem cells (HSCs) are an inevitable consequence of ageing. Some of these mutations disrupt the balance of stem-cell self-renewal and lead to detectable clonal expansions termed clonal haematopoiesis (CH). These detectable mutations provide rich information for understanding stem cell population sizes and dynamics. In this talk I will briefly describe how quantitative analyses of clone-size distributions from large-scale sequencing data obtained from hundreds of thousands of individuals can be used to provide estimates of stem cell population sizes and division rates as well as the biases in self-renewal caused by specific genetic alterations in blood. Our analyses reveal that most events driving clonal expansions in blood occur outside of canonical cancer-associated genes suggesting many “missing” driver mutations yet to be discovered. I will show how these missing drivers are able to resolve a deeply puzzling observation about the age-dependence of CH and outline ongoing work to identify possible epigenetic drivers of these clonal expansions.
Date: 22 June 2023, 13:00 (Thursday, 9th week, Trinity 2023)
Venue: MRC Weatherall Institute of Molecular Medicine, Headington OX3 9DS
Venue Details: WIMM Seminar Room & remotely via Teams
Speaker: Dr Jamie Blundell (Department of Oncology, Cambridge)
Organising department: MRC Weatherall Institute of Molecular Medicine
Organiser: Yasmine Saito (Weatherall Institute, University of Oxford)
Organiser contact email address: seminar.admin@imm.ox.ac.uk
Host: Professor Paresh Vyas (University of Oxford, Weatherall Institute of Molecular Medicine)
Part of: WIMM THURSDAY SEMINARS
Booking required?: Required
Booking email: seminar.admin@imm.ox.ac.uk
Audience: Members of the University only
Editors: Nicole Harris, Yasmine Saito