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The role of cytokine receptors in haematopoietic lineage specification

Objectif



I am interested in how growth factors regulate uni-lineage commitment and differentiation programmes in haematopoiesis i.e. do they (i) induce rate limiting changes and therefore specify lineage directly or (ii) simply promote the proliferation and/or maturation of cells that have already made commitment decisions in an independent manner. We will focus on the macrophage colony stimulating factor receptor (M-CSF-R) asking (i) can enforced M-CSF-R expression in multipotential cells instruct macrophage lineage specification and (ii) can the expression of tne MCSF-R in erythroid-committed cells block, or reverse, the erythroid-lineage specification programme and support a transdifferentiation of these cells into macrophages. In order to target the expression of human M-CSF-R to the desired haematopoietic compartments we will take a "knock-in" approach through homologous recombination in murine embryonic stem (ES) cells; we will target into the CD341stem cell antigen locus to obtain expression in multipotential cells and into the erythropoietin receptor locus to obtain expression in erythroid-committed cells.

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INSTITUTE OF CANCER RESEARCH : ROYAL CANCER HOSPITAL
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237,Fulham Road 237
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