Cowan CA, Atienza J, Melton DA, Eggan K.
Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells.
Science. 2005 Aug 26;309(5739):1369-73.
PubMed.
Cowan et al., in an elegant study published in Science, showed that human embryonic stem cells (ESCs) could be used to reprogram adult somatic cell nuclei. This result had added one more possibility to the methods of alternate derivation of ESC-like cells (Fig. 1) previously described.
Figure 1. Deriving ESCs from Fusion
The method described by Cowan et al. to generate ESC-like cells—fusion of a fibroblast and an ESC—represents one of several alternate methods for generating embryonic stem cells. Other methods include the use of somatic cell nuclear transfer, nonviable blastocysts, persistent pluripotent cells and transdifferentiation. [Image courtesy of Mahendra Rao]
The cells themselves are tetraploid and contain genomic information from both donor and recipient, and currently it is unclear how one could separate such genomic information. The present result also does not describe in detail how complete the activation of the ES cell program was and whether the somatic program was fully downregulated, as well.
Unlike previous results, however, the authors did perform a genomewide profiling, suggesting that the tetraploid cells were indeed more similar to ESCs than to fibroblasts from which the nuclei had been obtained. It is, though, difficult to obtain accurate quantification using arrays. Further, one needs to examine the epigenetic status of the lines, as well, to determine if the fidelity of reprogramming is truly adequate. Ultimately, it will be important to show that the reprogramming was sufficient that the resultant composite cell has all the properties characteristic of the ESC including absence of senescence, stability of telomeric ends, appropriate allele-specific gene expression, and appropriate patterns of microRNA regulation. Nevertheless, it confirms previous results that either the cytoplasm or the nucleus of ESCs can reprogram somatic nuclei.
And while it is unclear how useful tetraploid cells are for therapy, this result, in my mind, represents a significant advance and provides a very useful model to study what has been an otherwise intractable problem. I look forward to the identification of the reprogramming molecules and the dissection of the pathway and identification of the components that are critical. It is likely that these components can then be used to reprogram somatic nuclei in a relatively straightforward fashion.
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Life Technologies Corporation
Cowan et al., in an elegant study published in Science, showed that human embryonic stem cells (ESCs) could be used to reprogram adult somatic cell nuclei. This result had added one more possibility to the methods of alternate derivation of ESC-like cells (Fig. 1) previously described.
The cells themselves are tetraploid and contain genomic information from both donor and recipient, and currently it is unclear how one could separate such genomic information. The present result also does not describe in detail how complete the activation of the ES cell program was and whether the somatic program was fully downregulated, as well.
Unlike previous results, however, the authors did perform a genomewide profiling, suggesting that the tetraploid cells were indeed more similar to ESCs than to fibroblasts from which the nuclei had been obtained. It is, though, difficult to obtain accurate quantification using arrays. Further, one needs to examine the epigenetic status of the lines, as well, to determine if the fidelity of reprogramming is truly adequate. Ultimately, it will be important to show that the reprogramming was sufficient that the resultant composite cell has all the properties characteristic of the ESC including absence of senescence, stability of telomeric ends, appropriate allele-specific gene expression, and appropriate patterns of microRNA regulation. Nevertheless, it confirms previous results that either the cytoplasm or the nucleus of ESCs can reprogram somatic nuclei.
And while it is unclear how useful tetraploid cells are for therapy, this result, in my mind, represents a significant advance and provides a very useful model to study what has been an otherwise intractable problem. I look forward to the identification of the reprogramming molecules and the dissection of the pathway and identification of the components that are critical. It is likely that these components can then be used to reprogram somatic nuclei in a relatively straightforward fashion.
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