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Nuclear Reprogramming Development naturally progresses from totipotent fertilized eggs to pluripotent epiblast cells, to multipotent cells, and finally to terminally differentiated cells. According to Waddington's epigenetic landscape, this is analogous to a ball moving down a slope. The reversal of the terminally differentiated cells to totipotent or pluripotent cells (called nuclear reprogramming) can thus be seen as an uphill gradient that never occurs in normal conditions. However, nuclear reprogramming has been achieved using nuclear transplantation, or nuclear transfer (NT), procedures (often called "cloning"), where the nucleus of a differentiated cell is transferred into an enucleated oocyte. Although this is an. | Chapter 066. Stem Cell Biology Part 3 Nuclear Reprogramming Development naturally progresses from totipotent fertilized eggs to pluripotent epiblast cells to multipotent cells and finally to terminally differentiated cells. According to Waddington s epigenetic landscape this is analogous to a ball moving down a slope. The reversal of the terminally differentiated cells to totipotent or pluripotent cells called nuclear reprogramming can thus be seen as an uphill gradient that never occurs in normal conditions. However nuclear reprogramming has been achieved using nuclear transplantation or nuclear transfer NT procedures often called cloning where the nucleus of a differentiated cell is transferred into an enucleated oocyte. Although this is an error-prone procedure and the success rate is very low live animals have been produced using adult somatic cells as donors in sheep mouse and other mammals. In mice it has been demonstrated that ES cells derived from blastocysts made by somatic cell NT are indistinguishable from normal ES cells. NT can potentially be used to produce patient-specific ES cells carrying a genome identical to that of the patient. However the successful implementation of this procedure has not been reported in humans. Setting aside technical and ethical issues the limited supply of human oocytes will be a major problem for clinical applications of NT. Alternatively successful nuclear reprogramming of somatic cells by fusing them with ES cells has been demonstrated in mouse and human. However it is not yet clear how ES-derived DNA can be removed from hybrid cells. More direct nuclear reprogramming of somatic cells by transfecting specific genes or by exposing the cells to ES cell extracts is the subject of current research. Stem Cell Plasticity or Transdifferentiation The prevailing paradigm in developmental biology is that once cells are differentiated their phenotypes are stable. However a number of reports have shown that tissue stem cells which
