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Proceedings of the National Academy of Sciences of the United States of America
Jan 24, 2006;103 (4): 933-8.

ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable.

Tobias Brambrink, Konrad Hochedlinger, George Bell, Rudolf Jaenisch
Author Information
  1. Tobias Brambrink: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
PMID: 16418286 DOI: 10.1073/pnas.0510485103

Abstract

Reproductive cloning is uniformly rejected as a valid technology in humans because of the severely abnormal phenotypes seen in cloned animals. Gene expression aberrations observed in tissues of cloned animals have also raised concerns regarding the therapeutic application of "customized" embryonic stem (ES) cells derived by nuclear transplantation (NT) from a patient's somatic cells. Although previous experiments in mice have demonstrated that the developmental potential of ES cells derived from cloned blastocysts (NT-ES cells) is identical to that of ES cells derived from fertilized blastocysts, a systematic molecular characterization of NT-ES cell lines is lacking. To investigate whether transcriptional aberrations, similar to those observed in tissues of cloned mice, also occur in NT-ES cells, we have compared transcriptional profiles of 10 mouse NT- and fertilization-derived-ES cell lines. We report here that the ES cell lines derived from cloned and fertilized mouse blastocysts are indistinguishable based on their transcriptional profiles, consistent with their normal developmental potential. Our results indicate that, in contrast to embryonic and fetal development of clones, the process of NT-ES cell derivation rigorously selects for those immortal cells that have erased the "epigenetic memory" of the donor nucleus and, thus, become functionally equivalent. Our findings support the notion that ES cell lines derived from cloned or fertilized blastocysts have an identical therapeutic potential.

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Grants

  1. R01 HD045022/NICHD NIH HHS
  2. R37 CA084198/NCI NIH HHS
  3. R01-HD045022/NICHD NIH HHS
  4. R37-CA84198/NCI NIH HHS

MeSH Term

Animals
Blastocyst
Cell Culture Techniques
Cell Nucleus
Cloning, Organism
Cluster Analysis
Embryo, Mammalian
Epigenesis, Genetic
Fertilization
Fibroblasts
Gene Expression Regulation
Gene Expression Regulation, Developmental
Genetic Variation
Mice
Mice, Inbred C57BL
Models, Biological
Models, Genetic
Models, Statistical
Nucleic Acid Hybridization
Oligonucleotide Array Sequence Analysis
Stem Cells
Transcription, Genetic
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 10

Word Cloud

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