Figure 22–40 Production and pluripotency of eS cells. eS cells are derived from the inner cell mass (iCm) of the early embryo. the iCm cells are transferred to a culture dish containing an appropriate medium, where they become converted to eS cells and can be kept proliferating indefinitely without differentiating. the eS cells can be taken at any time—after genetic manipulation, if desired—and injected back into the inner cell mass of another early embryo. there they take part in formation of a well-formed chimeric animal that is a mixture of ordinary and eS-derived cells. the eS-derived cells can differentiate into any of the cell types in the body, including germ cells from which a new generation of mice can be produced. these next-generation progeny are no longer chimeric, but consist of cells that all inherit half their genes from the cultured eS cell line.
blastocyst develops in (blastocyst) clump of ES cells injected cells become foster mother into a healthy injected into incorporated in inner chimeric mouse; the ES cells may recipient blastocyst cell mass of host blastocyst contribute to any tissue cells. Grown in culture, these can be manipulated, by suitable choice of culture conditions, to give rise to large quantities of almost any type of differentiated cell, opening the way to important practical applications. Before discussing them, however, we consider the underlying biology.
a Core Set of transcription Regulators defines and maintains the  eS Cell State
What is it that gives ES cells and related types of pluripotent stem cells their extraordinary capabilities? What can they tell us about the fundamental mechanisms underlying stemness, cell differentiation, and the stability of the differentiated state?
For some attributes, the answer is simple. For example, an essential feature of ES cells is that they must avoid senescence. As discussed in Chapter 17, this is the fate of fibroblasts and many other types of somatic cells: they are limited in the number of times they will divide, in part at least because they lack telomerase activity, with the result that their telomeres become progressively eroded in each division cycle, leading eventually to cell-cycle arrest. ES cells, by contrast, express high levels of active telomerase, allowing them to escape senescence and continue dividing indefinitely. This is a property shared with other, more specialized types of stem cells, such as those of the adult intestine, which similarly can carry on dividing for hundreds or thousands of cycles.
The deeper problem is to explain how the whole complex pattern of gene expression in an ES cell is organized and maintained. As a first step, one can look for genes expressed specifically in ES cells or in the corresponding pluripotent cells of the early embryo. This approach identifies a relatively small number of candidate ES-critical genes; that is, genes that seem to be essential in one way or another for the peculiar character of ES cells. A gene called Oct4, for example, is exclusively expressed in ES cells and in related classes of cells in the intact organism—specifically, in the germ-cell lineage and in the inner cell mass and its precursors. Oct4 codes for a transcription regulator. When it is lost from ES cells, they lose their ES cell character; and when it is missing in an embryo, the cells that should specialize as inner cell mass are diverted into an extraembryonic pathway of differentiation and their development is aborted.
Fibroblasts Can be Reprogrammed to Create induced pluripotent Stem Cells (ipS Cells)