Using cell lines derived from the AGM-region in the mouse embryo it was possible to identify, by using gene expression arrays, Sfrp1, TGFb1 and TGFb3 as novel regulators of hematopoiesis. Mice deficient in Sfrp1 suffer from a wide range of significant hematopoietic abnormalities, even though none of them are lethal, such as: increased cell numbers in peripheral blood, increased numbers of phenotypical HSC in the bone marrow which also tended to be more in the G0/G1 phase of the cell cycle, increased production by hematopoietic progenitor cells, decreased amount of β-catenin, loss of HSC and MPP in serial bone marrow transplantations but no significant loss of function of HSC in limiting dilution transplantations. TGFb1 and TGFb3 were shown to enhance hESC hematopoietic differentiation and can further stimulate this process when added to cultures. In short, this thesis highlights novel ways for the microenvironment to regulate hematopoiesis.
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Using cell lines derived from the AGM-region in the mouse embryo it was possible to identify, by using gene expression arrays, Sfrp1, TGFb1 and TGFb3 as novel regulators of hematopoiesis. Mice deficient in Sfrp1 suffer from a wide range of significant hematopoietic abnormalities, even though none of them are lethal, such as: increased cell numbers in peripheral blood, increased numbers of phenotypical HSC in the bone marrow which also tended to be more in the G0/G1 phase of the cell cycle, incre...
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