There exists a clinical need for the production of platelets in vitro to help keep up with the existing demand used in transfusions. The use of human induced pluripotent stem cells (hiPSCs) to produce platelets is an attractive alternative to current sources, as they provide a potentially infinite source of cells. Our lab uses a technique we have termed ‘forward programming’ to produce mature megakaryocytes, the platelet precursor cell, from hiPSCs by overexpressing three key haematopoietic transcription factors (TFs), to drive differentiation. One of the major aims of my PhD is to improve our existing technique and move towards a more clinically compatible method, by generating a stable, inducible hiPSC line, for MK production. So far, I have demonstrated that the stoichiometric expression of these three TFs (FLI1, GATA1 and TAL1) generates a bipotent megakaryocyte-erythroid progenitor population, from which both megakaryocytes and red blood cells can be produced. I have demonstrated that inducible expression of a fluorescent protein in iPSCs is achievable by targeting a genomic safe harbour in iPSCs. This is an important breakthrough in stem cell technology, as this proof of principle demonstrates that a gene of interest can be inserted into the genome of iPSCs and expressed at a desired point in differentiation. We believe that these important findings will help to make the in vitro production of platelets more amenable to scaling-up, in order to move from the bench to the clinic.
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