Partial reprogramming of heterologous cells by defined factors to generate megakaryocyte lineage-restricted biomolecules
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(Published version)
Date
2018
Authors
Artuz, C.M.
Knights, A.J.
Funnell, A.P.W.
Gonda, T.J.
Ravid, K.
Pearson, R.C.M.
Quinlan, K.G.R.
Crossley, M.
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Journal article
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Biotechnology Reports, 2018; 20(e00285):e00285-1-e00285-4
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Crisbel M.Artuz, Alexander J.Knights, Alister P.W.Funnell, Thomas J.Gonda, Katya Ravid, Richard C.M.Pearson ... et al.
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Abstract
The ability of transcriptional regulators to drive lineage conversion of somatic cells offers great potential for the treatment of human disease. To explore the concept of switching on specific target genes in heterologous cells, we developed a model system to screen candidate factors for their ability to activate the archetypal megakaryocyte-specific chemokine platelet factor 4 (PF4) in fibroblasts. We found that co-expression of the transcriptional regulators GATA1 and FLI1 resulted in a significant increase in levels of PF4, which became magnified over time. This finding demonstrates that such combinations can be used to produce potentially beneficial chemokines in readily available heterologous cell types.
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© 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).