ZonMw TOP-grant for Catherine Robin

Catherine Robin, group leader at the Hubrecht Institute, receives a ZonMw TOP-grant for her project “Spatial and temporal gene expression patterns in the microenvironment promoting hematopoietic stem cell generation in vivo”. With this project, Catherine Robin and Alexander van Oudenaarden (co-applicant and director of the Hubrecht Institute) aim to identify new factors produced by the microenvironment and involved in the regulation of hematopoietic stem cells.

Every day, hematopoietic stem cells (HSCs) produce billions of new blood cells essential for life. Defects in HSCs lead to blood-related disorders and various cancers (e.g. anemia, leukemia). The transplantation of healthy donor HSCs to replace the patient defective ones is an important part of the treatment. Less than 30% of the patients have matched donors in their family. Therefore successful transplantation in most patients relies on finding unrelated volunteer donors with the highest compatibility (the chance of an optimal match being very low). Since the number of transplantations increases every year, the availability of HSCs has become a major hurdle. To circumvent this shortage, extensive efforts have been made to expand donor HSCs ex vivo or to generate new sources of HSCs in vitro (e.g. from pluripotent stem cells or somatic cells). Success has been limited so far mainly because the extrinsic events promoting HSC production in vivo remain largely unknown, and therefore difficult to reproduce in vitro. Identifying the regulatory factors produced by the aortic microenvironment, which constitutes the initial physiological niche for HSC generation during embryonic development, would certainly help to design optimal in vitro HSC culture conditions in the future.

The goal of Robins’ project is to use the genome-wide RNA tomography technique (tomo-seq) developed by the van Oudenaarden-lab to combine RNA-Sequencing data and spatial information. With this approach, they will accurately determine spatial gene expression patterns in the aorta of various embryo species, isolated at different developmental stages. It will allow to identify conserved key genes and pathways that control and regulate HSC generation in restricted regions of the aorta.

This project will contribute to advance our knowledge of the complex network of factors and pathways involved in the microenvironment supporting HSC production in vivo. It should prove useful in the future for engineering appropriate in vitro culture conditions to produce autologous HSC grafts needed to treat inherited and acquired blood disorders.