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Marella de Bruijn
Professor of Developmental Haemopoiesis
- Director of Graduate Studies
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.
Transcriptional regulation of Hhex in hematopoiesis and hematopoietic stem cell ontogeny.
Migueles RP. et al, (2017), Dev Biol, 424, 236 - 245
Runx transcription factors in the development and function of the definitive hematopoietic system.
de Bruijn M. and Dzierzak E., (2017), Blood, 129, 2061 - 2069
Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Luis TC. et al, (2016), Nat Immunol, 17, 1424 - 1435
Turning it down a Notch
De Bruijn M., (2016), Blood, 128, 1541 - 1542
Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells.
Pereira CF. et al, (2016), Dev Cell, 36, 525 - 539