HSCORIGIN
From mesoderm to hematopoietic stem cell commitment: cellular and molecular events occuring during mouse embryonic development
| Coordinatore | KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Netherlands [NL] |
| Totale costo | 1˙500˙000 € |
| EC contributo | 1˙500˙000 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2012-StG_20111109 |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-03-01 - 2018-02-28 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Organization address
address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS contact info |
NL (AMSTERDAM) | hostInstitution | 1˙500˙000.00 |
| 2 |
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Organization address
address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS contact info |
NL (AMSTERDAM) | hostInstitution | 1˙500˙000.00 |
Mappa
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Obiettivo del progetto (Objective)
'Hematopoietic Stem Cells (HSCs) are at the origin of all blood cells needed throughout life. HSC transplantation is used to treat patients with blood related disorders. However, the number of HSCs available for clinic and research remains limited. The production of large quantities of HSCs in vitro, for example by reprogramming or transdifferentiation of somatic cells to a HSC stage, would be a good solution, but this remains extremely difficult. To overcome these problems, we must understand all the molecular and cellular events underlying the in vivo HSC formation. Because all adult HSCs are initially produced during embryonic development, it is clear that studying how HSCs are generated during ontogeny is of importance. We and others have demonstrated that specialized endothelial cells endowed with a hemogenic potential produce all HSCs. However, the exact anatomical site(s) of mammalian HSC origin and all steps leading to HSC production are unclear and highly controversial. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation to answer these fundamental questions. I first propose to develop a totally novel in vivo embryo rescue assay to unambiguously determine the exact site(s) of HSC origin. In this assay, candidate precursors will be tested for HSC potential by a novel in utero transplantation technique performed directly into developing HSC-deficient embryos. We will also determine how hemogenic endothelial cells generate HSCs (directly or via an intermediate population). Gene expression profiles and comparative analyses of these populations will be performed by RNA-Sequencing to determine the dynamic changes in gene expression and to identify key players in the HSC commitment process. I anticipate that our studies will significantly advance our understanding of normal HSC generation, and help to produce HSCs in vitro. Furthermore, it should also lead to a better comprehension of HSC dysfunction in diseases.'