Figure 22–44 Factors that have been observed to enhance reprogramming efficiency. emphasized here are those factors that can alter chromatin states, with those in the top three rows having the most direct effects. an up arrow indicates that reprogramming is increased when the activity of the indicated factor is increased; a down arrow indicates that reprogramming is increased when the activity of the indicated factor is decreased. thus, for example, increased activity of histone acetyl transferases and increased activity of histone deacetylases have opposite effects, as expected from their biochemical activities (see p. 196).
Figure 22–45 Production of differentiated cells from eS or iPS cells in culture.
these cells can be cultured indefinitely as pluripotent cells when attached as a monolayer to a dish. alternatively they can be detached and allowed to form aggregates called embryoid bodies, which causes the cells to begin to specialize. Cells from embryoid bodies, cultured in media with different factors added, can then be driven to differentiate in various ways. (based on e. Fuchs and J.a. Segre, Cell 100:143–155, 2000. with permission from elsevier.) macrophage colony-interleukin-3, stimulating factor, interleukin-1 macrophage iPS cells (about 1,000 cells) dibutyryl cAMP, retinoic acid smooth muscle cell fbroblast fbroblast fbroblast growth factor 2, growth factor 2, growth epidermal platelet-derived factor growth factor growth factor 1258 Chapter 22:  Stem Cells and tissue Renewal aggregate of hollow ball of budding of optic vesicle invaginates cultured ES cells neural cells optic vesicle to form optic cup (B) 100 µm
Figure 22–46 Cultured eS cells can give rise to a three-dimensional organ. (a) Remarkably, under appropriate conditions, mouse eS cells in culture can proliferate, differentiate, and interact to form a three-dimensional, eye-like structure, which includes a multilayered retina similar in organization to the one that forms in vivo. (b) Fluorescent micrograph of an optic cup formed by eS cells in culture. the structure includes a developing retina, containing multiple layers of neural cells, which produce a protein (pink) that serves as a marker for retinal tissue. (b, from m. eiraku, n. takata, h. ishibashi et al., Nature 472:51–56, 2011. with permission from macmillan publishers ltd.)
Cells of one Specialized type Can be Forced to transdifferentiate directly into another
The route we have just described, from one mode of differentiation to another via conversion to an iPS cell, seems needlessly roundabout. Could we not convert cell type A into cell type B directly, without backtracking to the embryonic-like iPS state? For many years, it has been known that such transdifferentiation can be achieved in a few special cases, such as the conversion of fibroblasts into skeletal muscle cells by forced expression of MyoD (see p. 396). But now, with the insights that have come from the study of ES and iPS cells, ways are being found to bring about such interconversions in a much wider range of cases.