Differentiation of human embryonic stem cells into mesoderm progenitorcells by controlling the TGF-b and WNT signaling pathway

Tran Ngoc Tung

Human embryonic stem (hES) cells have a unique ability to proliferate unlimitedly while maintaining the pluripotency (capability of differentiating into all cell types of human body). The pluripotency of human embryonic stem cells is regulated by the co-operation of many intracellular signaling pathways such as: TGF-b and WNT signaling pathways. In this paper, we investigated the function of two these signaling pathways in differentiation ability of hES cells. Human embryonic stem cells were cultured under the feeder-free condition in condition medium containing Activin A (5ng/ml) and BIO (2mM) (6-bromoindirubin-3'-oxime) - the activators of TGF-b and WNT signaling pathways respectively. After 3 days, mesoderm progenitor cell marker genes such as Brachuyry, goosecoid, MIXL1, and wnt3 were highly expressed, while the pluripotency-associated gene markers (Oct4, nanog) were down-regulated. This cell population can further differentiate into mesenchymal stem cells derived from mesoderm progenitor cells. In conclusion, the activation of these two signaling pathway induced hES cells to differentiate into mesoderm progenitors.