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11) The recent Nobel Prize in Physiology or Medicine was awarded based on two sets of
experiments. The first of these is described in the following abstract:
An important problem in embryology is whether the differentiation of cells depends upon a
stable restriction of the genetic information contained in their nuclei. The technique of nuclear
transplantation has shown to what extent the nuclei of differentiating cells can promote the
formation of different cell types. Yet no experiments have so far been published on the
transplantation of nuclei from fully differentiated normal cells. This is partly because it is
difficult to obtain meaningful results from such experiments. The small amount of cytoplasm
in differentiated cells renders their nuclei susceptible to damage through exposure to the
saline medium, and this makes it difficult to assess the significance of the abnormalities
resulting from their transplantation. It is, however, very desirable to know the developmental
capacity of such nuclei, since any nuclear changes which are necessarily involved in cellular
differentiation must have already taken place in cells of this kind. The experiments described
below are some attempts to transplant nuclei from fully differentiated cells. Many of these
nuclei gave abnormal results after transplantation, and several different kinds of experiments
have been carried out to determine the cause and significance of these abnormalities. The
donor cells used for these experiments were
intestinal epithelium cells of feeding tadpoles.
This is the final stage of differentiation of
many of the endoderm cells whose nuclei
have already been studied by means of
nuclear transplantation experiments in
Xenopus. The results to be described here
may therefore be regarded as an extension of
those previously obtained from differentiating
endoderm cells.
11 A) What explanation would you give for
these results? What has changed in the
nuclei? What does the table at the right
tell us about the genetics of development?
(10 points)
The second experiment is described in the following abstract:
Successful reprogramming of differentiated human somatic cells into a pluripotent state
would allow creation of patient- and disease-specific stem cells. We previously reported
generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from
mouse somatic cells by transduction of four defined transcription factors. Here, we
demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same
four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human
embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression,
epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore,
these cells could differentiate into cell types of the three germ layers in vitro and in teratomas.
These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
11 B) What does this tell you about the nature of the changes that take place during the
process of differentiation? How would you think that the reactivation of these genes might

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