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Visualizing the molecular control of blood - stroma interactions at the single cell level

Final Activity Report Summary - VB-SINT (Visualizing the molecular control of blood - stroma interactions at the single cell level)

The microenvironment of a hematopoietic stem cell (HSC) has a critical influence on its survival and behaviour. However, despite intense research, it remains unclear how the microenvironment influences HSCs. Previous analyses were based on the observation of static time points lacking constant observation of the dynamic interactions of HSCs with their microenvironment. We have therefore established novel bio-imaging systems allowing the long-term observation of HSCs in stromal niches at the single cell level. Stromal cell lines with or without the potential to support HSC self-renewal was used as 'stem cell' and 'differentiation' niches. HSC differentiation was detected in real-time by novel approaches for long-term live antibody staining in living cell cultures.

Niche dependent behaviour of HSCs or more mature multi-potent progenitor cells was quantified by precisely measuring the survival, generation time, adhesion, migration and differentiation of HSCs and their progeny. We show that niche derived signals influence survival, cell cycle progression and differentiation of HSCs. In addition, our results are compatible with an intrinsic model of HSC asymmetric self-renewal. These results lay ground for the identification of niche derived molecular signals influencing HSC fates, and for the analysis of their integration with varying HSC intrinsic molecular states.