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Partial reprogramming of heterologous cells by defined factors to generate megakaryocyte lineage-restricted biomolecules.

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.

SUBMITTER: Artuz CM

PROVIDER: S-EPMC6197760 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Partial reprogramming of heterologous cells by defined factors to generate megakaryocyte lineage-restricted biomolecules.

Artuz Crisbel M CM Knights Alexander J AJ Funnell Alister P W APW Gonda Thomas J TJ Ravid Katya K Pearson Richard C M RCM Quinlan Kate G R KGR Crossley Merlin M

Biotechnology reports (Amsterdam, Netherlands) 20181002

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 signi ...[more]

PMID: 30364711

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