Knockdown of H19 Enhances Differentiation Capacity to Epidermis of Parthenogenetic Embryonic Stem Cells

Parthenogenetic embryonic stem (pES) cells are pluripotent stem cells derived from artificially activated oocytes without embryo destruction, thus eliciting less ethic concerns, and have been demonstrated promising for autologous stem cell therapy. However, pES cells could carry inappropriate imprinting such as relatively high expression of H19, a paternal imprinted gene, and may negatively influence their lineage differentiation. We show that knockdown of H19 by shRNA in mouse pES cells does not alter self-renewal and expression of genes associated with pluripotency. We find that down-regulation of H19 promotes differentiation of pES cells to epidermis. In addition, H19 depletion also facilitates differentiation of pES cells to cardiomyocytes and strong heart-like beating. Our data support the notion that reduction of H19 improves pES cell differentiation in the lineages of ectoderm and mesoderm, and provide further evidence suggesting that defective imprinting can be manipulated to allow potential application of pES cells for stem cell therapy.