CORDIS
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CORDIS

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Identifying spatial determinants of immune cell fate commitment

Project information

Grant agreement ID: 818846

Status

Ongoing project

  • Start date

    1 July 2019

  • End date

    30 June 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 997 500

  • EU contribution

    € 1 997 500

Hosted by:

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

Objective

The complex architecture of the mammalian hematopoietic system has been studied for decades, yet the molecular mechanisms underlying cell fate commitment remain poorly understood. Although cytokine signals are major determinants of hematopoietic cell fate, only few niches of stem and progenitor cells have been characterized. Here, we propose to resolve the cell type composition of mouse bone marrow by integrating single-cell RNA-seq with high-resolution spatial analysis of gene expression in tissue sections, visualizing ~250 cell type specific markers by multiplexed single-molecule RNA fluorescent in situ hybridization. This approach will reveal preferential co-localization of hematopoietic cells with other bone marrow-resident cell types, and globally predict niches of hematopoietic progenitor sub-types to pinpoint microenvrionmental determinants of hematopoietic cell fate. Based on this reference we will investigate the role of the microenvironment in the pathogenesis of myelodysplastic syndromes (MDS), representing one of the most frequent blood cell malignancies, commonly giving rise to leukaemia with poor prognosis. To investigate conservation of microenvironmental determinants of normal and malignant hematopoietic differentiation in human, we will apply the same strategy to healthy donors and human MDS patients and compare predicted cell types, differentiation trajectories, and niche interactions to those derived from healthy mice and murine MDS models. This approach will reveal conserved niche regulators of cell fate commitment involved in disease pathogenesis, which we will functionally analyse in murine models to identify novel therapeutic targets for prevention and treatment of MDS. Our approach represents a blueprint for investigating human malignancies of under-characterized tissues by applying cutting-edge high-resolution techniques in combination with advanced computational methods to jointly analyse the murine model and human patient microenvironment.

Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Address

Hofgartenstrasse 8
80539 Muenchen

Germany

Activity type

Research Organisations

EU Contribution

€ 1 997 500

Beneficiaries (1)

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 1 997 500

Project information

Grant agreement ID: 818846

Status

Ongoing project

  • Start date

    1 July 2019

  • End date

    30 June 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 997 500

  • EU contribution

    € 1 997 500

Hosted by:

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany