Differentiation of Embryonic Stem Cell Lines Generated from Adult Somatic Cells by Nuclear Transfer

Wakayama, Teruhiko; Tabar, Viviane; Rodríguez, Iván; Perry, Anthony C.F.; Studer, Lorenz; Mombaerts, T. Peter

doi:10.1126/science.1059399

Cited by 525 publications

(335 citation statements)

References 17 publications

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“…5). Individual blastocysts from various somatic cells have been used to derive ES cells, but the success rate is about 4%, compared to an average of 40-50% from normal blastocysts of the 129/Sv strain 70 . Derivation of ES cells is apparently unaffected by the lack of imprints, as these cells were obtained from blastocysts generated with the imprint-free (and substantially demethylated) PGC nuclei 30 .…”

Section: Are Imprints Essential For Development?mentioning

confidence: 99%

Reprogramming of genome function through epigenetic inheritance

Surani

2001

Nature

412

296

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Most cells contain the same set of genes and yet they are extremely diverse in appearance and functions. It is the selective expression and repression of genes that determines the specific properties of individual cells. Nevertheless, even when fully differentiated, any cell can potentially be reprogrammed back to totipotency, which in turn results in re-differentiation of the full repertoire of adult cells from a single original cell of any kind. Mechanisms that regulate this exceptional genomic plasticity and the state of totipotency are being unravelled, and will enhance our ability to manipulate stem cells for therapeutic purposes.

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Section: Are Imprints Essential For Development?mentioning

confidence: 99%

Reprogramming of genome function through epigenetic inheritance

Surani

2001

Nature

412

296

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“…14,15 Cloned mice were even produced by using natural killer T (NKT) cells. 16 NKT cells were shown to have the same developmental potential as adult fibroblasts and cumulus cells 17 but greater than lymphocytes. 18 In general, the use of fetal and adult somatic cells in nuclear transfer is extremely inefficient in producing live offspring.…”

Section: Introductionmentioning

confidence: 95%

Correlation of Developmental Differences of Nuclear Transfer Embryos Cells to the Methylation Profiles of Nuclear Transfer Donor Cells in Swine

Bonk¹,

Cheong²,

Li³

et al. 2007

Epigenetics

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Methylation of DNA is the most commonly studied epigenetic mechanism of developmental competence and somatic cell nuclear transfer (SCNT). Previous studies of epigenetics and the SCNT procedures have examined the effects of different culture media on donor cells and reconstructed embryos, and the methylation status of specific genes in the fetus or live offspring. Here we used a microarray based approach to identify the methylation profiles of SCNT donor cells including three clonal porcine fetal fibroblast-like cell sublines and adult somatic cells selected from kidney and mammary tissues. The methylation profiles of the donor cells were then analyzed with respect to their ability to direct development to the blastocyst stage after nuclear transfer. Clonal cell lines A2, A7 and A8 had blastocyst rates of 11.7% a , 16.7% ab and 20.0% b , respectively ( ab p < 0.05). Adult somatic cells included kidney, mammary (large), and mammary (small) also had different blastocyst rates ( ab p < 0.05) of 4.2% a , 10.7% ab and 18.3% b , respectively. For clonal donor cells and for adult somatic cell groups the donor cells with the highest blastocyst rates also had methylation profiles with the lowest similarity to the methylation profiles of the in vivo-produced blastocysts. Conversely, the donor cells with the lowest blastocyst rates had methylation profiles with the highest similarity to the methylation profiles of the in vivo-produced blastocysts. Our findings show there is an inverse correlation to the similarity of the methylation profiles of the donor cells and the in vivo-produced embryos, and to the blastocyst rates following SCNT. ABBREVIATIoNSA2, A7, A8, designation for three different donor cell populations; ANOVA, analysis of variance; BSA, bovine serum albumin;

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“…Cells or tissue derived by this pathway would have nuclear DNA identical to the patient's and, therefore, would likely not be subject to immune rejection [1][2][3]. In cows and mice, NT technology and ES cell derivation have been used successfully in combination to establish ES or ES-like cell lines from reprogrammed somatic cell nuclei [4][5][6][7], and mouse ntES cells have been shown to be fully pluripotent [7].…”

Section: Introductionmentioning

confidence: 99%

Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes

Chen¹,

Liu

et al. 2003

Cell Res

200

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To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.

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Differentiation of Embryonic Stem Cell Lines Generated from Adult Somatic Cells by Nuclear Transfer

Cited by 525 publications

References 17 publications

Reprogramming of genome function through epigenetic inheritance

Reprogramming of genome function through epigenetic inheritance

Correlation of Developmental Differences of Nuclear Transfer Embryos Cells to the Methylation Profiles of Nuclear Transfer Donor Cells in Swine

Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes

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