Page 21

The Developmental Origins of Blood Stem Cells Blood stem cells (BSCs) have been intensely studied for many decades as a model system for stem cell biology. Our work focuses on the emergence and regulation of the first BSCs in the mouse embryo in order to identify the basic mechanisms that control their generation from precursor cells and their initial expansion and dissemination to the different blood-generating organs. Knowledge of these early regulatory pathways has proven to be invaluable for understanding how adult BSCs can be manipulated for clinical purposes and how interference with these processes may result in blood-related disorders. Our research therefore complements that of several groups on the Addenbrookes site which also work on various aspects of normal and leukaemic stem cell biology. Adult-type BSCs are first detected at day 10.5 during mouse development in a region of the embryo around the main aorta that is known as the AGM region. A day later these cells can also be detected in the yolk sac and the foetal liver. Our previous work has identified the placenta as another organ that harbours BSCs during development. We have recently further defined the region of the AGM where BSCs are first detected and have used thsi information to carry out screening experiments which resulted in the identification of novel regulators of BSC generation in the AGM. Furthermore, we have unveiled a functional interplay between the embryonic blood and nervous systems which develop in close proximity. More recently, we have also started focussing on how these pathways are corrupted in infant leukaemia.

Emergence of blood stem cells (green) from the wall of the aorta (red).

Key Publications Fitch S.R., Kimber G., Wilson N.K., Parker A., Mirshekar-Syahkal B., GĂśttgens B., Medvinsky A., Dzierzak E. & Ottersbach K. (2012). Signaling from the sympathetic nervous system regulates hematopoietic stem cell emergence during embryogenesis. Cell Stem Cell 11:554-566 PMID: 23040481

Katrin Ottersbach Katrin Ottersbach obtained her undergraduate degree in Biochemistry at the University of Edinburgh in 1997. She carried out her PhD research at the Beatson Institute for Cancer Research in Glasgow under the supervision of Prof. Gerard Graham. After completion of her PhD in 2001, she moved to Rotterdam, Netherlands, to take up a postdoctoral position in the group of Prof. Elaine Dzierzak. In 2006, she moved to the University of Cambridge, UK, to set up her own lab at the Cambridge Institute for Medical Research She became a Principal Investigator in the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute when it was formed in 2012.

Funding Wellcome Trust MRC British Society for Haematology Kay Kendall Leukaemia Fund Leukaemia & Lymphoma Research

Mascarenhas M.I., Parker A., Dzierzak E. & Ottersbach K. (2009). Identification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling. Blood 114:4645-53 PMID: 19794138 Ottersbach K. & Dzierzak E. (2005). The Murine Placenta Contains Hematopoietic Stem Cells within the Vascular Labyrinth Region. Developmental Cell 8:377-87 PMID: 15737933

Group Members Chrysa Kapeni Maria Mascarenhas Neil Barrett Wendi Bacon Simon Fitch Camille Malouf Kankan Xia

19

Cambridge Stem Cell Institute Brochure 2012  
Cambridge Stem Cell Institute Brochure 2012