Although different cell types may transcribe different parts of the genome, for the most part the genome is identical in all cells. Segments of the genome are rearranged and lost during development of the T and B lymphocytes of the immune system from hematopoietic precursors (see Chapter 23), but most somatic cells appear to have an intact genome, equivalent to that in the germ line. Evidence that at least some somatic cells have a complete and functional genome comes from the successful production of cloned animals by nuclear transfer. In this procedure, often called somatic-cell nuclear transfer (SCNT), the nucleus of an adult somatic cell is introduced into an egg whose nucleus has been removed; the manipulated egg, which contains the diploid number of chromosomes and is equivalent to a zygote, is then implanted into a foster mother. The only source of genetic information to guide development of the embryo is the nuclear genome of the donor somatic cell. The low efficiency of generating cloned animals by SCNT, combined with a high frequency of diseases such as obesity in the animals that are cloned, however, raises questions about how many adult somatic cells do in fact have a complete functional genome and whether those that do can be completely reprogrammed into a pluripotent undifferentiated state. Even the successes, such as the famous cloned sheep “Dolly,” have some medical problems. Even if differentiated cells have a physically complete genome, clearly only parts of it are transcriptionally active (see Chapter 9). A cell could, for example, have an intact genome, but be unable to properly reactivate specific genes due to inherited chromatin epigenetic states.

Further evidence that the genome of a differentiated cell can revert to having the full developmental potential characteristic of an ES cell comes from experiments in which olfactory sensory neurons—postmitotic cells that normally will not divide again—were genetically marked with green fluorescence protein (GFP) and then used as donors of nuclei (Figure 21-7). When the nuclei from differentiated olfactory sensory neurons were implanted into enucleated mouse oocytes, a small fraction of them developed into blastocysts that produced GFP. The blastocysts were used to derive ES cell lines, which were then used to generate mouse embryos. These embryos, derived entirely from olfactory sensory neuron genomes, formed healthy green-fluorescing mice. Thus, at least in some cases, the genome of a differentiated cell can be reprogrammed completely to form all tissues of a mouse.