A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic stem cells

Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, are pluripotent and continue to self-renew. To better understand the molecular mechanisms underlying self-renewal, we have been searching for a gene(s) which is specifically expressed in self-renewing ES cells. Here we report the isolation and characterization of a novel gene, Sddr (stem cell-derived differentiation regulator). Sddr was highly expressed in undifferentiated ES cells, and its expression was downregulated upon differentiation. In addition to ES cells, Sddr expression was observed strongly in ovary, and weakly in lung. Immunostaining and cellular fractionation analyses suggested that Sddr is a cytoplasmic protein associated with the cytoskeleton. Sddr-null ES cells showed no remarkable abnormalities in their undifferentiated state. In contrast, in differentiating Sddr-null cells, induction of several differentiation-associated markers was enhanced, and downregulation of self-renewal marker genes was accelerated, as compared with wild-type cells. These results suggest that although it is dispensable for ES cell self-renewal, Sddr is a negative regulator of ES cell differentiation.