Equivalency of Nuclear Transfer‐Derived Embryonic Stem Cells to Those Derived from Fertilized Mouse Blastocysts
Sayaka Wakayama,Martin L. Jakt,Masako Suzuki,Ryoko Araki,Takafusa Hikichi,Satoshi Kishigami,Hiroshi Ohta,Nguyen Van Thuan,Eiji Mizutani,Yuko Sakaide,Sho Senda,Satoshi Tanaka,Mitsuhiro Okada,Masashi Miyake,Masumi Abe,Shin-Ichi Nishikawa,Kunio Shiota,Teruhiko Wakayama +17 more
TL;DR: Compared to blastocyst‐derived ESCs, the similarities of NT‐ESCs and ESCs indicate that murine therapeutic cloning by somatic cell NT can provide a reliable model for preclinical stem cell research.
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Abstract: Therapeutic cloning, whereby nuclear transfer (NT) is used to generate embryonic stem cells (ESCs) from blastocysts, has been demonstrated successfully in mice and cattle. However, if NT-ESCs have abnormalities, such as those associated with the offspring produced by reproductive cloning, their scientific and medical utilities might prove limited. To evaluate the characteristics of NT-ESCs, we established more than 150 NT-ESC lines from adult somatic cells of several mouse strains. Here, we show that these NT-ESCs were able to differentiate into all functional embryonic tissues in vivo. Moreover, they were identical to blastocyst-derived ESCs in terms of their expression of pluripotency markers in the presence of tissue-dependent differentially DNA methylated regions, in DNA microarray profiles, and in high-coverage gene expression profiling. Importantly, the NT procedure did not cause irreversible damage to the nuclei. These similarities of NT-ESCs and ESCs indicate that murine therapeutic cloning by somatic cell NT can provide a reliable model for preclinical stem cell research.
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Citations
Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming
Rudolf Jaenisch,Richard A. Young +1 more
TL;DR: In this article, the authors review strategies to reprogram somatic cells to a pluripotent embryonic state and discuss their understanding of the molecular mechanisms of reprogramming based on recent insights into the regulatory circuitry of the PLSTM.
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TL;DR: This review summarizes the progress that has been made in the iPSC field over the last 4 years, with an emphasis on understanding the mechanisms of cellular reprogramming and its potential applications in cell therapy.
Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning.
Xiangzhong Yang,Sadie L. Smith,X. Cindy Tian,Harris A. Lewin,Jean-Paul Renard,Teruhiko Wakayama +5 more
TL;DR: The recent literature on nuclear reprogramming by SCNT is reviewed, including studies of gene expression, DNA methylation, chromatin remodeling, genomic imprinting and X chromosome inactivation, which seems to be highly efficient.
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Mechanisms and models of somatic cell reprogramming
TL;DR: Recent discoveries regarding the role of reprogramming factors in remodelling the genome are discussed, including new insights into the function of MYC, and the different phases, markers and emerging models ofReprogramming are described.
Totipotency, pluripotency and nuclear reprogramming.
Shoukhrat Mitalipov,Don P. Wolf +1 more
TL;DR: Two major approaches to reprogramming are summarized: (1) somatic cell nuclear transfer and (2) direct reprograming using genetic manipulations.
References
Preserving the genetic integrity of human embryonic stem cells.
Maisam Mitalipova,Raj R. Rao,Deborah M Hoyer,Julie A. Johnson,Lorraine F. Meisner,Karen Louise Jones,Stephen Dalton,Stephen L Stice +7 more
TL;DR: The impact of TRIPS on either the commercial strategies of foreign companies or their strategic alliances with Indian companies is anyone’s guess, as it is only one parameter among many that will be used in making foreign investment decisions.
478
Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei
David Humpherys,Kevin Eggan,Hidenori Akutsu,Adam Friedman,Konrad Hochedlinger,Ryuzo Yanagimachi,Eric S. Lander,Todd R. Golub,Rudolf Jaenisch +8 more
TL;DR: The authors' results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus.
Cloned mice have an obese phenotype not transmitted to their offspring
Kellie L.K. Tamashiro,Teruhiko Wakayama,Hidenori Akutsu,Yukiko Yamazaki,Jennifer Lachey,Matthew D. Wortman,Randy J. Seeley,David A. D'Alessio,Stephen C. Woods,Ryuzo Yanagimachi,Randall R. Sakai +10 more
TL;DR: It is reported that the increased body weight of cloned B6C3F1 female mice reflects an increase of body fat in addition to a larger body size, and that these mice share many characteristics consistent with obesity.
Early death of mice cloned from somatic cells.
Narumi Ogonuki,Kimiko Inoue,Yoshie Yamamoto,Yoko Noguchi,Kentaro Tanemura,Osamu Suzuki,Hiroyuki Nakayama,Kunio Doi,Yukiko Ohtomo,Michiko Satoh,Akira Nishida,Atsuo Ogura +11 more
TL;DR: The lifespan of mice cloned from somatic cells is significantly shorter than that of genotype- and sex-matched controls, most likely due to severe pneumonia and hepatic failure, demonstrating the possibility of long-term deleterious effects of somatic-cell cloning, even after normal birth.
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