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<https://discovery.ucl.ac.uk/id/eprint/18691> <http://purl.org/dc/terms/title> "The effect of bone morphogenetic protein 4 on haematopoietic stem cells"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/18691> <http://purl.org/ontology/bibo/abstract> "Bone morphogenetic protein-4 (BMP4) is highly expressed at sites of haematopoietic stem cell (HSC) formation. During HSC formation in humans, BMP4 is strongly expressed by\r\ncells underlying the ventral floor of the dorsal aorta. BMP4 in combination with other\r\nfactors has been shown to play a role in haematopoietic differentiation. The genes Runx1,\r\nScl, Gata2 and Lmo2 are vital to the development of the haematopoietic system, and\r\ndeletion of these genes produces an embryonic lethal phenotype due to the absence of\r\nblood formation. This study investigated whether BMP4 alone upregulates the expression\r\nof these genes. The role of BMP4 was explored during HSC development in an embryonic\r\nstem (ES) cell differentiation model and at later developmental stages using ex vivo foetal\r\nliver and bone marrow serum free cultures. Differentiating ES cells cultured in serum-free\r\nmedium were found to express BMP4 and the BMP receptor endogenously. To establish a\r\nmodel for exogenous BMP4 addition in isolation, lentiviral vectors were used to deliver\r\nshort hairpin RNA (shRNA) for sustained RNAi knockdown of endogenous Bmp4\r\nexpression during ES cell differentiation. Differentiating shRNA treated ES cells were\r\ncultured and the expression of Runx1, Scl, Gata2 and Lmo2 was measured over time by\r\nreal time reverse transcription PCR. With the addition of exogenous BMP4 alone,\r\nexpression of Runx1, Scl, Gata2 and Lmo2 was unchanged at days 2 and 4 but increased at\r\nday 6 of differentiation. This demonstrates that BMP4 up regulates the expression of these\r\ngenes which are critical to the development of the haematopoietic system. The use of\r\nlentiviral shRNA knockdown provides a model for the control of endogenous growth\r\nfactors in future investigations of growth factors in ES cell differentiation."^^<http://www.w3.org/2001/XMLSchema#string> .
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