Project description
The bone marrow niche in health and disease
Haematopoietic stem cells reside in a specific microenvironment of the bone marrow known as a niche. The niche encompasses different types of cells, the extracellular matrix, and paracrine factors that collectively support the undifferentiated state and self-renewal capacity of stem cells. The EU-funded SyLeNCe project is interested in dissecting the interaction between niche components during homeostasis and disease. Emphasis will be given to the detailed characterisation of cell relationships during malignant transformation in leukaemia as well as disease development and progression. The SyLeNCe work will offer a more holistic view of the stem cell niche and may unveil new candidates for the treatment of leukaemia.
Objective
Our understanding of the different layers of organization in tissues remains limited. Stem cell niches offer a tightly controlled environment and a unique opportunity to look into this question. Reductionist approaches have been proven highly efficient dissecting the complexity of stem cell niches in a unidirectional fashion. However, this approach fails to recognize the tri-dimensional complexity of tissue organization. Hence we propose a systems biology approach based on low input and single cell RNA sequencing of bone marrow niche populations in order to establish not only the molecular landscape of cells that comprise the stem cell niche in homeostasis and disease but also the lineage relationships that may exist between cells in the stroma. Using the mouse bone marrow niche during neoplastic transformation to acute myeloid leukemia (AML), we will first unravel the cellular and molecular interactions that constitute the tumor microenvironment during disease development and progression using multi parametric flow cytometry and RNA-sequencing. Information gathered from these experiments will also provide a list of molecular candidates for therapeutic intervention in AML. We will validate those candidate cell populations and genetic pathways by means of gain and loss-of-function assays in vitro and in vivo using murine models and primary human AML samples. Completion of our interdisciplinary project will provide, for the first time a complete transcriptional and cellular map of a tissue, revealing the heterotypic interactions that define the real nature of a tissue. Perhaps then we could start to appreciate the elegant complexity of the ecosystem that the stem cell and its niche share. I hope SyLeNCe will facilitate the description of novel vulnerabilities that could be explored therapeutically for the treatment of acute myeloid leukaemia having an impact on the quality of life and long-term survival of AML patients.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences ecology ecosystems
- natural sciences biological sciences genetics RNA
- medical and health sciences clinical medicine oncology leukemia
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
31008 Pamplona
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.