Haematopoiesis is a unique experimental system to study thee biology of stem cells. Blood is formed by different cell types that are produced all along the life of the individual, thanks to the existence of the haemtopoietic stem cells (HSC). The phenotypic characteristics and blood differentiation potential of HSC have been extensively analyzed from adults. However studies during development have shown additional levels of complexity related to the unique differentiation properties of embryonic/foetal HSC and also related to the close relationship during development of the haematopoietic and vascular system.
 

The focus of my research in the last years was the study of the properties that characterize HSC at different stages of development. The approach I undertook was to characterize enhancers active in HSC and the use of these regulatory elements in expression vectors in vivo to the biology of HSC.

In recent work I used regulatory elements from the SCL gene (stem cell leukaemia gene), a transcription factor important for blood and vasculature formation. During this work we have established that the SCL 3' enhancer is specific for HSC, haematopoietic progenitors and vascular endothelium. This enhancer is active in embryonic/foetal stages and also in adults suggesting a conserved regulatory mechanism of SCL during development in HSC. Also, I used the 3'Enh to drive expression of SCL in SCL-/- mutant embryos resulting in the rescue of the blood and endothelial phenotype and demonstrating the functionality of this enhancer .

This work also revealed an essential role of SCL in erythropoiesis. Current studies focus in three lines of work:

- Notch signaling pathway in HSC biology by manipulation of Notch family members expression by the 3' enhancer,
- Contribution potential of HSC to vascular endothelium during development,
- Characterization of new HSC enhancer from SCL, an ongoing collaboration with the Cambridge group.

Future work will continue to explore the differentiation potential of HSC during development in combination with the analisys of genes relevant to HSC biology and their targeted expression driven by HSC-enhancers.