The embryonic stem (ES) cell is special. If we knew what gave it the power to create all the cell types of the body (pluripotency), we might be able to create new ES cells and use them to repair damaged tissues. Two lines of research have added significantly to our understanding of the molecular basis of pluripotency.

Dr Magdalena Zernicka-Goetz and colleagues at the Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology in Cambridge have located a master switch that controls one of the earliest choices a cell can make. They identified a crucial molecular difference between cells in the four-cell mouse embryo, much earlier than expected.

This difference is a chemical tag (a methyl group) added to the histone proteins, which package DNA in the chromosomes. Tagging just one amino acid in a particular histone (H3) switches on genes that establish and maintain pluripotency. When this modification was introduced into embryonic cells, their daughter cells were pluripotent – showing dramatic activation of pluripotency-associated genes, such as Nanog.

Research from Professor Austin Smith 1 and colleagues at the Institute for Stem Cell Research in Edinburgh suggests that Nanog has a central role in pluripotency.

When ES cells are fused with other cells, the resulting cell may be converted to a pluripotent state. Broadly speaking, the more differentiated the cell, the less likely it is to become pluripotent after fusion. When ES cells containing higher than normal levels of Nanog were used, however, the efficiency of conversion of part-differentiated cells was greatly increased.

So, although not the only player, Nanog is clearly a powerful driver of pluripotency.

Image: An early embryo broken open to reveal stem cells; Yorgos Nikas

External links

• Torres-Padilla ME et al. Histone arginine methylation directs cells towards pluripotency in the early mouse embryo. Nature 445, 214-218.
• Silva J et al. Nanog promotes transfer of pluripotency after cell fusion. Nature 2006;441(7096):997–1001.

1 Now at the Wellcome Trust Centre for Stem Cell Research, University of Cambridge.