Members of the miR-290 cluster modulate in vitro differentiation of mouse embryonic stem cells

作者：Zovoilis Athanasios^*; Smorag Lukasz; Pantazi Angeliki; Engel Wolfgang

来源：Differentiation, 2009, 78(2-3): 69-78.

DOI：10.1016/j.diff.2009.06.003

• Embryonic stem cells
• MicroRNAs
• Differentiation
• Dppa-3
• Brachyury
• Dkk-1

We report the biological effects of miR-290 cluster via gain-of-function or loss-of-function experiments in mouse embryonic stem cells (ESCs) cultured under differentiation conditions. Under these conditions we found that overexpression of miR-290 cluster in ESCs cannot prevent downregulation of Oct-4, but inhibition results in earlier down regulation of Oct-4 compared with the negative control. In consistence with previous findings that report ectopic expression of Brachyury during gastrulation in Argonaute-2 KO mice due to impaired miRNA function, we show that miR-290 cluster regulates negatively differentiation of ESCs towards mesodermal and germ cell lineage. These results suggest that although incapable to maintain pluripotent state alone, miR-290 cluster inhibits ESC differentiation and it is involved in the pathways controlling mesoderm and primordial germ cell differentiation. Finally, we provide proofs that members of this cluster target Dkk-1 gene, a Wnt pathway inhibitor, and affect this pathway, which can partially explain why miR-290 cluster favours pluripotency against differentiation.

• 出版日期2009-10