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Role of Transforming Growth Factor Signalling in Marrow Stem Cell Differentiation

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Bone marrow stem cells have the ability to self renew and differentiate into a multitude of different cell types. Of the various cell potentials, the endothelial differentiation process has been the least understood due to highly context dependent methods of regulation. It was previously found that following mesodermal induction, endothelial precursors emerged in association with inhibited transforming growth factor beta (TGFβ) signalling. To better understand the role of TGFβ signalling in the differentiation process, we treated bone marrow mononuclear cells with either a TGFβ pathway inhibitor, GW788388, or exogenous activating ligand, TGFβ1, and characterized the expression levels of various cellular markers. We demonstrate that neither treatment leads directly to an endothelial phenotype. Instead, we propose a two-step process of TGFβ and bone morphogenic protein (BMP) signalling cross-talk, that could potentially be responsible for endothelial differentiation of bone marrow derived stem cells. Our ability to derive functional endothelial cells from postnatal stem cells may impact multiple fields of research, including the study of vascular regeneration and understanding the mechanisms underlying vascular disease.

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