Prof Marella de Bruijn
|Research Area:||Developmental and Stem Cell Biology|
|Technology Exchange:||Cell sorting, ES cell / homologous recombination, Flow cytometry, Immunohistochemistry, In situ hybridisation, Microscopy (Confocal), Mouse models, Transcript profiling and Transgenesis|
|Scientific Themes:||Developmental Biology & Stem Cells and Haematology|
|Keywords:||Hematopoietic stem cells, Hemogenic endothelium, Developmental biology, Lineage specification and Transcriptional regulation|
A central question in the stem cell field is what are the cellular and molecular mechanisms that underlie the generation and maintenance of the different types of stem cells. The focus of our research is the origin of the haemopoietic stem cells (HSCs) during mouse embryonic development. The first HSCs appear in the aorta-gonad-mesonephros (AGM) region and in the vitelline and umbilical arteries of the midgestation mouse embryo. Runx1, the gene encoding the DNA- binding subunit of the heterodimeric transcription factor Runx1:CBFb, is expressed at these sites prior to the generation of functional HSCs, and is absolutely required for HSCs generation. The specific temporal and spatial pattern of Runx1 expression suggests a critical role for Runx1 in the specification of precursor cells towards the haemopoietic lineage and in the establishment and maintenance of haemopoietic differentiation programs. It also suggests that factors regulating the expression of Runx1 are important to the development of the haemopoietic system. Because of its pivotal position at the onset of haemopoiesis, our lab uses Runx1 as an entry point for studies aimed at building a roadmap of HSC development in the embryo and identifying the signals and transcription factors required for HSC specification and maintenance. These studies provide a basis for building gene regulatory networks underlying HSC specification. Such insights are expected to contribute to the development of new therapeutic strategies for blood-related disorders. RUNX1 mutations are involved in human leukaemia, and a deeper understanding of the role of Runx1 in the regulatory network underlying HSC emergence could also shed light the molecular mechanisms of leukaemia onset and progression.
|Prof Berthold Gottgens||Cambridge Stem Cell Institute||University of Cambridge||United Kingdom|
|Dr John Pimanda||University of New South Wales, Sydney||Australia|
|Prof Roger Patient||Nuffield Division of Clinical Laboratory Sciences||Oxford University, Weatherall Institute of Molecular Medicine||United Kingdom|
|Prof Catherine Porcher||Nuffield Division of Clinical Laboratory Sciences||University of Oxford||United Kingdom|
|Prof Sten Eirik Jacobsen||Nuffield Division of Clinical Laboratory Sciences||Oxford University, Weatherall Institute of Molecular Medicine||United Kingdom|
|Prof Thomas Milne||Nuffield Division of Clinical Laboratory Sciences||Oxford University, Weatherall Institute of Molecular Medicine||United Kingdom|
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