A Tetraploid Twist on the Embryonic Stem Cell
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《新英格兰医药杂志》
The production of human embryonic stem cells by somatic-cell nuclear transfer depends on a profound but obscure event that takes place when the nucleus of a "donor" somatic cell is injected into an enucleated ovum (see diagram). Somehow, the cytoplasm of the oocyte reprograms the chromosomes of the somatic cell's nucleus so that the newly formed cell becomes pluripotent. The cell develops into a blastocyst, from which embryonic stem cells can be derived that carry a set of chromosomes identical to that of the donor. The "tailored" embryonic stem cells thus derived have fueled hope for new treatments for degenerative diseases such as type 1 diabetes and Parkinson's disease. They are believed to be pluripotent — that is, they can differentiate, under appropriate conditions, into cells of any type. With a nuclear complement that is identical to that found in the somatic-cell donor, they are unlikely to be rejected by that donor.
Derivation of Patient-Specific Embryonic Stem Cells by Nuclear Transfer (Panel A) and Derivation of a Tetraploid Cell with Properties of an Embryonic Stem Cell (Panel B).
Human embryonic stem cells derived by transfer of the nucleus from a somatic cell (Panel A) are considered to have therapeutic potential, in contrast with the tetraploid cells recently described by Cowan et al. (Panel B).1 These tetraploid cells were generated by the fusion of a fibroblast and an embryonic stem cell and have the behavioral properties of an embryonic stem cell.
In a recent study, Cowan and colleagues1 tested the hypothesis that, like the oocyte's cytoplasm, the human embryonic stem cell can also reprogram the chromosomes of a somatic cell. They encouraged the fusion of fibroblasts and embryonic stem cells by coculturing cells of both types in an agent that facilitates membrane fusion, and they obtained stable tetraploid hybrid cells, each of which had a single nucleus (see diagram). These cells looked and behaved like embryonic stem cells. For example, a protein characteristic of embryonic stem cells was expressed from RNA transcribed from a fibroblast chromosome; the cells seemed to be immortal (they have been passaged more than 50 times). They developed and differentiated into embryoid bodies (in vitro) and teratomas (in vivo) — each of these had tissues expressing markers characteristic of each of the three germ-cell layers (endoderm, mesoderm, and ectoderm). Thus, the hypothesis would seem to be correct: human embryonic stem cells can reprogram adult somatic-cell chromosomes after cell fusion. Additional support is provided by similar findings previously obtained with mouse cells.
There is some risk that people who are seeking to place restrictions on research into the biology of human embryonic stem cells may misinterpret these findings, arguing that the new technique represents an alternative approach to the generation of "chromosomally tailored" human embryonic stem cells that have therapeutic potential. Kevin Eggan, one of the investigators in this study, says he is "very disappointed" by this prospect and emphasizes that the study "does not deliver a methodology that can replace human embryonic stem cells." Although this finding will inspire further studies to identify and determine the mechanism of action of the critical factors that reprogram chromosomes, the hybrid cells cannot generate embryonic stem cells and, because they are tetraploid, their therapeutic potential is nil.(Elizabeth G. Phimister, P)
Derivation of Patient-Specific Embryonic Stem Cells by Nuclear Transfer (Panel A) and Derivation of a Tetraploid Cell with Properties of an Embryonic Stem Cell (Panel B).
Human embryonic stem cells derived by transfer of the nucleus from a somatic cell (Panel A) are considered to have therapeutic potential, in contrast with the tetraploid cells recently described by Cowan et al. (Panel B).1 These tetraploid cells were generated by the fusion of a fibroblast and an embryonic stem cell and have the behavioral properties of an embryonic stem cell.
In a recent study, Cowan and colleagues1 tested the hypothesis that, like the oocyte's cytoplasm, the human embryonic stem cell can also reprogram the chromosomes of a somatic cell. They encouraged the fusion of fibroblasts and embryonic stem cells by coculturing cells of both types in an agent that facilitates membrane fusion, and they obtained stable tetraploid hybrid cells, each of which had a single nucleus (see diagram). These cells looked and behaved like embryonic stem cells. For example, a protein characteristic of embryonic stem cells was expressed from RNA transcribed from a fibroblast chromosome; the cells seemed to be immortal (they have been passaged more than 50 times). They developed and differentiated into embryoid bodies (in vitro) and teratomas (in vivo) — each of these had tissues expressing markers characteristic of each of the three germ-cell layers (endoderm, mesoderm, and ectoderm). Thus, the hypothesis would seem to be correct: human embryonic stem cells can reprogram adult somatic-cell chromosomes after cell fusion. Additional support is provided by similar findings previously obtained with mouse cells.
There is some risk that people who are seeking to place restrictions on research into the biology of human embryonic stem cells may misinterpret these findings, arguing that the new technique represents an alternative approach to the generation of "chromosomally tailored" human embryonic stem cells that have therapeutic potential. Kevin Eggan, one of the investigators in this study, says he is "very disappointed" by this prospect and emphasizes that the study "does not deliver a methodology that can replace human embryonic stem cells." Although this finding will inspire further studies to identify and determine the mechanism of action of the critical factors that reprogram chromosomes, the hybrid cells cannot generate embryonic stem cells and, because they are tetraploid, their therapeutic potential is nil.(Elizabeth G. Phimister, P)