Objective
Newly formed mature hematopoietic cells are generated through a complex maturation process based on the differentiation of Hematopoietic Stem Cells (HSC). In the mouse embryo, HSCs are first detected in the Aorta-Gonade-Mesonephros (AGM) region at midgestation.
They arise from the major arteries and are thought to differentiate from a population of hemogenic endothelial cells (EC). Cellular events that occur during AGM-associated hematopoiesis are well-documented, but the underlying molecular mechanisms are still under investigation. The overall objective of the present project is to further our understanding of molecular regulations governing early production of HSCs from hemogenic ECs.
It is focused on the RUNX1 transcription factor, a key regulator of HSC production and a frequent target in human haematological malignancies. In mouse embryo, disruption of either Runx1 or its co-factor Cbfb leads to complete failure in HSC development. RUNX1 is known to govern this process at the level of hemogenic ECs and to mark all HSCs at midgestation.
However, since the requirement of CBFb in this process is poorly understood and the accurate function of RUNX1 is not known, the specific aims of this project are:
1) To describe the expression of the RUNX1 binding partner, CBFb, in midgestation aortic HSCs and ECs
2) To conditionally knockout Runx1 during different stages of the EC to HSC transition in the midgestation aorta.
For this purpose, transgenic mouse models will be generated and AGM-associated hematopoiesis will be analysed using a large panel of descriptive and functional approaches. Innovative methodologies will be undertaken to analyse the complex biological activity of RUNX1.
We will use fluorescent markers to follow genes expression and cell fate and also design a Cre-loxP recombination systems to conditionally disrupt Runx1 function. This study will allow us to explore in detail biological activity and function of both RUNX1 and CBFb in HSCs production.
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.
- natural sciences biological sciences developmental biology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine obstetrics
- medical and health sciences clinical medicine embryology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
FP6-2004-MOBILITY-5
See other projects for this call
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.
Coordinator
ROTTERDAM
Netherlands
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.