Mapping the molecular landscape of early blood stem cell emergence

The study team, led by Professor Alexander Medvinsky, used a powerful technique to map which genes are switched on in which cells and in which location. By doing so, they identified some of the key genetic and molecular players controlling development of early blood stem cells also known as haematopoietic stem cells (HSCs). This knowledge could help improve laboratory production of such cells for future blood stem cell therapies.

Haematopoietic stem cells in the bone marrow supply mature blood cells over the entire life. In 2011, the Medvinsky group found that these stem cells emerge in a specific area of the early embryo called the aorta-gonad-mesonephros (AGM) region and the researchers focussed on this region. The process of haematopoietic stem cells development is choreographed by the complex action of genes and cell interactions in the AGM region.

In the current study, Medvinsky, Dr Edie Crosse and colleagues used a combination of advanced genetic analysis techniques based on so called transcriptomics technologies. The researchers obtained a snapshot of the genes that have been switched on in the developing HSCs and in surrounding cells in the AGM region.

The team identified the protein endothelin 1 as an important secreted regulator of human haematopoietic stem cell development. The map of which genes are expressed where will also be a valuable resource for other scientists to design future studies of HSC development.

This study provides an insight into the molecular mechanisms underpinning the development of human haematopoietic stem cells. It will allow scientists to develop and test new ideas about how this complex process is controlled. The results of this study could help improve the generation of HSCs in the laboratory, and thereby improve future development of HSC therapies.

This work was supported by Medical Research Council UK and was published in the journal Cell Stem Cell.

Cell Stem Cell article, Crosse et al.