Bonnet lab Haematopoietic Stem Cell Laboratory
: Areas of interest
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The haematopoietic (blood) system produces billions of mature blood cells every day. In order to maintain the homeostasis of the system, a tight regulation is thus in place. Our lab is interested in understanding the regulation of the haematopoietic stem cells (which produce all the mature cells for the entire life of an individual), both in normal development and during leukaemia. We are specifically interested in the extrinsic mechanisms that regulate these cells and how we could intervene in order to eradicate the leukaemic stem cell.
The laboratory is interested in studying both normal human haematopoietic stem cells (HSCs) and leukaemic stem cells (LSCs). As an assay for the activity of these cells, we perform xenotransplantation into a NOD/SCID (non-obese diabetic/severe combined immunodeficient) mouse model. Comparison of the resulting engraftment phenotype, and investigation of the molecular pathways regulating cellular functions, especially self-renewal, are the focus of the group.
We are also investigating the relationship between normal HSC, LSC and their microenvironment. We have developed in vivo imaging techniques allowing us to visualise and define the normal and leukaemic stem cell niche. We have developed a 3D scaffold system where human stroma cells could be co-cultured in vivo with HSC or LSC to study the effect of the interaction and study the cross-talk between stroma and HSC/LSC. All these projects should shed light into pathways or interactions that are more specifically used by LSC cells and, thus, where therapeutic intervention might be developed.
Figure 1: (A) Transversal section of a tibia showing in purple the bone and in red vessels. This shows the complex and dense vascularisation in long bone even in the zone close to the bone (endosteal region) thought to be devoid of vessels. (B) 3D tracking of human leukaemia (HL60 cell line) in live bone marrow.
