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Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning

Nature Genetics volume 39, pages 295–302 (2007)Cite this article

A Corrigendum to this article was published on 01 October 2007

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Abstract

Therapeutic cloning, whereby somatic cell nuclear transfer (SCNT) is used to generate patient-specific embryonic stem cells (ESCs) from blastocysts cloned by nuclear transfer (ntESCs), holds great promise for the treatment of many human diseases. ntESCs have been derived in mice and cattle, but thus far there are no credible reports of human ntESCs. Here we review the recent literature on nuclear reprogramming by SCNT, including studies of gene expression, DNA methylation, chromatin remodeling, genomic imprinting and X chromosome inactivation. Reprogramming of genes expressed in the inner cell mass, from which ntESCs are derived, seems to be highly efficient. Defects in the extraembryonic lineage are probably the major cause of the low success rate of reproductive cloning but are not expected to affect the derivation of ntESCs. We remain optimistic that human therapeutic cloning is achievable and that the derivation of patient-specific ntESC lines will have great potential for regenerative medicine.

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Figure 1: Efficiency of blastocyst development, ESC line derivation and embryo term development in mice and cattle.
Figure 2: Methylation dynamics during normal early embryonic development and in clones, adapted from ref. 27.
Figure 3: X chromosome inactivation in the ICM and TE lineages of normal and cloned mouse embryos.
Figure 4: Efficiency of tetraploid complementation with ESCs derived from fertilized (fESCs) and embryos cloned by nuclear transfer (ntESCs).

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  • 26 September 2007

    In the version of this article initially published, the legend for Figure 1 is inaccurate. The original legend for Figure 1c failed to note that the cells derived from cattle embryos were embryonic stem cell (ESC)-like trophectoderm cell colonies. The full legend for Figure 1c should read “Therapeutic cloning: percentage ESC line derivation (mice) or ESC-like trophectoderm cell colony formation (cattle) from embryos derived from both IVF and nuclear transfer." This error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

Much appreciation is due to C. Jennings for many discussions, comments and editorial assistance on this manuscript and to M. Watanabe for her assistance in preparation of the manuscript. This work was partially funded by grants from the US Department of Agriculture.

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Authors and Affiliations

  1. Sadie L. Smith and X. Cindy Tian are at the Center for Regenerative Biology and Department of Animal Science, Xiangzhong Yang, University of Connecticut, Storrs, Connecticut 06269, USA. xiangzhong.yang@uconn.edu,

    Xiangzhong Yang, Sadie L Smith & X Cindy Tian

  2. Harris A. Lewin is at the Department of Animal Sciences and Institute for Genomic Biology, University of Illinois, Urbana, Illinois 61801, USA.,

    Harris A Lewin

  3. Jean-Paul Renard is at the Unite Mixte de Recherche Biologie du Developpement et Reproduction, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France.,

    Jean-Paul Renard

  4. Teruhiko Wakayama is at the Center for Developmental Biology, RIKEN Kobe, 650-0047, Japan.,

    Teruhiko Wakayama

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Yang, X., Smith, S., Tian, X. et al. Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nat Genet 39, 295–302 (2007). https://doi.org/10.1038/ng1973

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