Nuclear reprogramming by somatic cell nuclear transfer--the cattle story

Somatic cell nuclear transfer (cloning) returns a differentiated cell to a totipotent status; a process termed nuclear reprogramming. Nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. To understand the deficiencies of nuclear reprogramming, our research has focused on both candidate genes (imprinted and X-linked genes) and global gene expression patterns in cloned bovine embryos/offspring as compared to those generated by conventional reproduction. We found aberrant expression patterns of H19 and Igf2r as well as X-linked genes in term cloned calves. The expression profiles of cloned blastocysts, however, closely resembled those of the naturally fertilized embryos but were considerably different from those of their nuclear donor cells. Our findings suggest that cloned embryos have undergone significant nuclear reprogramming by the blastocyst stage. However, it is possible that during re-differentiation in later development gene expression aberrancies occur. Additionally, small initial nuclear reprogramming errors may be manifested during subsequent development.