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Research

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.

Katrin Ottersbach

Group leader
Chancellor's fellow / Senior lecturer / LLR Bennett senior fellow
0131 651 9500
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Aims and areas of interest

The main interest of our group 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.

Image left: expression of three microenvironmental regulators of HSC emergence around the E11.5 mouse embryonic dorsal aorta. Image right: clusters of emerging ckit  haematopoietic cells in the dorsal aorta of an E11.5 mouse embryo.

Collaborators