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RXR IN MYELOID CELLS

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Contribution of RXRs to myeloid cell biology from hematopoietic stem cells to o...

Contribution of RXRs to myeloid cell biology from hematopoietic stem cells to osteoclastogenesis Hematopoietic stem cells (HSCs) yield blood precursors devoted to unilineage differentiation and production of mature blood cells, including red blood cells, megakaryocytes, lymphocytes and myeloid cells. Precursors of the myeloid... ver más

31/08/2013

CENTRO NACIONAL DE...

45K€

Presupuesto del proyecto: 45K€

Líder del proyecto

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASC... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 28M€

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-08-31 No tenemos la información de la convocatoria

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Líder del proyecto

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASC... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 28M€

Presupuesto del proyecto 45K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Hematopoietic stem cells (HSCs) yield blood precursors devoted to unilineage differentiation and production of mature blood cells, including red blood cells, megakaryocytes, lymphocytes and myeloid cells. Precursors of the myeloid lineage differentiate into monocytes and granulocytes but at given stages of their maturity they can be also sources of multinucleated osteoclasts. Consequently, any altered myelopoiesis can be directly linked to deficiencies in osteclastogenesis and impaired bone homeostasis. Retinoic X receptors (RXRa, RXRb and RXRg) are members of the nuclear receptor family. They appear to contribute to hematopoiesis and osteoclastogenesis via their roles as heterodimeric partners of several nuclear receptors. Functionally the most important isotype is RXRa during morphogenesis. Since RXRs can function either as homodimers or heterodimers, it is unclear whether the effects of RXRs on hematopoiesis and osteoclastogenesis are coupled to RXR homodimers, heterodimers, or involve the regulation of parallel pathways. Additionally, in mouse models of RXRa deletion, a partial redundancy in RXRa, b and g functions can be also observed. In this context, the goal of the presented project is to characterize the role of RXRs in HSC differentiation and osteoclastogenesis. In this project we will work with a knockout mouse model in which both RXRa and RXRb are selectively ablated in the hematopoietic system. Using this model we will be able to characterize the in vivo effects of the conditional inhibition of RXRa and b in the murine hematopoietic system and we can clarify the contribution of each isoforms to myeloid cell differentiation and osteoclastogenesis. The results are anticipated to open new perspectives for developing stem cell based therapies for the treatment of bone-related diseases such as osteoporosis or rheumatoid arthritis, nowadays affecting hundreds of millions of people worldwide.

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