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HSCS AND HIF

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Cerrado

The role of hypoxia inducible factors in human haematopoietic stem cell biology...

The role of hypoxia inducible factors in human haematopoietic stem cell biology and leukaemogenesis Mammalian haematopoiesis in the adult takes place predominantly in the bone marrow (BM) where a population of haematopoietic stem cells (HSC) are located. HSC are able to self-renew and give rise to all the blood cell types. The f... ver más

08/01/2013

CR-UK

173K€

Presupuesto del proyecto: 173K€

Líder del proyecto

CANCER RESEARCH UK LBG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-01-08 No tenemos la información de la convocatoria

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1 Participantes

CR-UK

0.00€ | Lider

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Líder del proyecto

CANCER RESEARCH UK LBG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 173K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Mammalian haematopoiesis in the adult takes place predominantly in the bone marrow (BM) where a population of haematopoietic stem cells (HSC) are located. HSC are able to self-renew and give rise to all the blood cell types. The fate choice of HSC to either self-renew or differentiate is controlled by an interplay between intrinsic mechanisms and extrinsic signals from the surrounding environment called stem cell niche. The existence of a hypoxic niche in the BM has been highlighted in the last decade. It has been proposed that the most quiescent HSC reside in the most hypoxic areas in the BM suggesting that low oxygen levels might play a key role in the maintenance of HSC. However the molecular mechanisms by which HSC respond to hypoxia have not been elucidated. Cells have developed a molecular mechanism for oxygen sensing. An important mediator is the transcriptional complex hypoxia-inducible factor (HIF). At low oxygen levels, HIF is stabilized and regulates the transcription of crucial genes involved in cell proliferation, survival and differentiation. Under normoxia, HIF has a low transcriptional activity. In addition, HIF has been reported to be upregulated in certain pathological conditions such as cancer where a high expression of HIF correlates with a poor prognosis. The aim of this project is to understand the molecular mechanisms by which human HSC response to their hypoxic environment. I will address this question by studying the role of HIF in HSC. I will first concentrate on analysing the consequences that genetically manipulating HIF might have on HSC in vitro and in vivo. Secondly I will analyse whether HIF is upregulated in leukemic stem cells (LSC) and in such a case, I will finally investigate the consequences that downregulating HIF might have in the modulation of leukaemia. Defining the role of HIF in HSC and LSC will provide for the first time a molecular link between the hypoxic niche, HSC maintenance and leukaemia development in humans.

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