Objective
The cells forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear. Our recent studies have demonstrated that mesenchymal stem cells (MSC) identified using expression of the intermediate filament protein nestin constitute an essential HSC niche component. Nestin+ cells contribute to bone formation, contain all the mesenchymal activity and can self-renew and expand in serial transplantations. Nestin+ MSC are spatially associated with HSC and fibres from the sympathetic nervous system, and highly express HSC maintenance genes. These genes and others triggering nestin+ MSC differentiation are selectively downregulated during enforced HSC mobilisation or β3-adrenoceptor activation. Parathormone treatment doubles bone marrow nestin+ cells and favours their osteoblastic differentiation. In contrast, in vivo nestin+ MSC depletion rapidly mobilises HSC from the bone marrow to extramedullary sites. Purified HSC rapidly home near nestin+ MSC in the bone marrow of lethally irradiated mice, whereas in vivo nestin+ MSC depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem cell types and argue for a unique niche in the bone marrow. Nestin+ MSC sharing some properties with the ones previously characterised in post-natal bone marrow are present in the foetal liver. In this proposal, we will characterise specific functions nestin+ cells in the adult HSC niche, and will analyse the role of nestin+ MSC during developmental HSC migration. We will also study the homeostatic regulation of the bone marrow stem-cell niche by analysing the role of autonomic and hormonal signals on the proliferation and fate of MSC and HSC. These studies will offer insight into the homeostatic regulation of a somatic stem-cell niche and uncover potential therapeutic targets to stimulate skeletal regeneration and HSC homing, engraftment and mobilisation.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine transplantation
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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.
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.
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.
FP7-PEOPLE-2011-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
28029 Madrid
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.