Developmental origins of blood stem cells and leukaemia Blood stem cells have the ability to produce every blood cell type and are therefore of immense clinical importance. Our group investigates how these cells are first generated during foetal development, how they can be maintained and what their unique properties are. A further interest of our group is how these early blood cells are targeted by mutations that can lead to cancer development in infant patients. Professor Katrin Ottersbach Professor of Developmental Haematology / Cancer Research UK Fellow Contact details Website: Personal profile Work: 0131 651 9500 Email: katrin.ottersbach@ed.ac.uk Haematopoietic cells in the mouse embryonic dorsal aorta (E11.5). Left: expression of three microenvironmental regulators of haematopoietic stem cell emergence. Right: clusters of emerging ckit haematopoietic cells Aims and areas of interestOne major part of my group's research is to understand how the first haematopoietic stem cells (HSCs) are generated during development and how their subsequent expansion, migration and differentiation are regulated. A particular focus in this context is the identification of the cellular and molecular composition of the microenvironment that facilitates the emergence of HSCs and how this composition changes as HSCs mature and migrate in the developing foetus. The ultimate aim is to dissect out the specific components required for particular HSC functions so that the right conditions can be recreated to achieve HSC generation, expansion and differentiation in vitro. We have recently demonstrated that the transcription factor Gata3 via its role in the sympathetic nervous system is required for HSC production, thus functionally linking these two co-developing systems.We are continuing our studies on how exactly catecholamines, the mediators of the sympathetic nervous system, act on emerging HSCs. We also have evidence that Gata3 performs additional functions during HSC emergence which we are currently investigating.Embryonic and foetal haematopoietic cells have unique properties with respect to proliferation response and differentiation bias. These are important in the context of HSC expansion and certain types of infant leukaemia that have a prenatal origin, and are another area of interest in the lab. We are particularly interested in infant leukaemias that have chromosomal rearrangements at the MLL locus as these have a particularly poor prognosis. Using MLL-AF4 and MLL-AF9 as examples, our aim is to characterise the foetal-specific context that contributes to disease development and how these oncofusions compromise normal blood development. The overall aim is to identify more specific therapeutic targets and to develop faithful in vivo models in which these can be tested. Studying the developmental origins of infant leukaemia Publications Publications Group members Giuseppina Camiolo, Research FellowAlasdair Duguid, TRACC Clinical LecturerEwan Egan, Martin Lee Doctoral Scholarship StudentHelene Jakobczyk, Postdoctoral Research AssociateTom Leah, Research AssistantRagini Medhi, BioinformaticianChris Mullen, PhD Student Funders Cancer Research UKWorldwide Cancer ResearchMRCBlood Cancer UK Collaborators Professor Juerg Schwaller, University Hospital Basel, SwitzerlandDr Chris Halsey, University of GlasgowDr Kristina Kirschner, University of GlasgowProfessor Rose Zamoyska, University of EdinburghDr Karen Keeshan, University of GlasgowProfessor Pablo Menendez, University of Barcelona, SpainProfessor Thomas Milne, University of Oxford This article was published on 2024-02-26
