FP6Individual fellowship2007–2009

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

FP6 — Marie Curie Actions (Human Resources and Mobility)

Duration
2007-11-01 → 2009-05-31
EU contribution
€149,722
Participants
1
Scheme
IIF

Lines connect the coordinator with its partners.

Results in brief

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.

Data: CORDIS, © European Union

Project objective

The behaviour of hematopoietic cells is influenced by their microenvironment. These niches" are composed of variety of cells, including stromal cells. As cells mature, they move from one niche to another within the bone marrow until they are released into the periphery. To further understand these interactions, we will utilize a novel, non-invasive computer-driven microscopy program to visualize the interaction of blood cells with stromal cells at the single cell level.Stromal cells lines have been previously generated from fetal liver and one such cell line has been shown to support primitive blood cells. We will directly compare the interaction of immature and mature blood cells on this stromal cell line and other stromal cell lines that d o not maintain immature blood cells. By doing this, we hope to understand how hematopoietic cells behave on these cells and what interactions occur to keep blood cells immature, or how they are induced to mature.To further understand the factors involved in the interaction of blood cells with different niches, we will introduce the expression of growth factors into stromal cells and assess their effect on hematopoietic differentiation and movement. We will also eliminate the expression of growth factors to find out the effect of the loss of these proteins on blood cell behaviour."

Original text from CORDIS.

Participants

  • HELMHOLTZ ZENTRUM MUENCHEN, DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT · MUENCHEN NEUHERBERGCoordinatorGermany

Links

Data: CORDIS, © European Union