Heterozygous Embryonic Stem Cell Lines Derived from Nonhuman Primate Parthenotes

Monoparental parthenotes represent a potential source of histocompatible stem cells that should be isogenic with the oocyte donor and therefore suitable for use in cell or tissue replacement therapy. We generated five rhesus monkey parthenogenetic embryonic stem cell (PESC) lines with stable, diploi...

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Published in:Stem cells (Dayton, Ohio) Vol. 26; no. 3; pp. 756 - 766
Main Authors: Dighe, Vikas, Clepper, Lisa, Pedersen, Darlene, Byrne, James, Ferguson, Betsy, Gokhale, Sumita, Penedo, M. Cecilia T., Wolf, Don, Mitalipov, Shoukhrat
Format: Journal Article
Language:English
Published: Bristol John Wiley & Sons, Ltd 01.03.2008
Subjects:
Animals
Cell Differentiation
Cell Line
Cell Separation
DNA Methylation
Embryo, Mammalian
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Female
Fertilization in Vitro
Gene Expression Regulation
Genomic Imprinting
Genotype
Heterozygote
Histocompatibility
Histocompatible
Humans
Imprinting
Macaca mulatta
Macaca mulatta - embryology
Meiotic recombination
Microsatellite Repeats - genetics
Parthenogenesis
Parthenogenetic
Polymorphism, Single Nucleotide - genetics
Prader-Willi Syndrome - genetics
Primates
ISSN:1066-5099, 1549-4918, 1549-4918
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Summary:Monoparental parthenotes represent a potential source of histocompatible stem cells that should be isogenic with the oocyte donor and therefore suitable for use in cell or tissue replacement therapy. We generated five rhesus monkey parthenogenetic embryonic stem cell (PESC) lines with stable, diploid female karyotypes that were morphologically indistinguishable from biparental controls, expressed key pluripotent markers, and generated cell derivatives representative of all three germ layers following in vivo and in vitro differentiation. Interestingly, high levels of heterozygosity were observed at the majority of loci that were polymorphic in the oocyte donors. Some PESC lines were also heterozygous in the major histocompatibility complex region, carrying haplotypes identical to those of the egg donor females. Expression analysis revealed transcripts from some imprinted genes that are normally expressed from only the paternal allele. These results indicate that limitations accompanying the potential use of PESC‐derived phenotypes in regenerative medicine, including aberrant genomic imprinting and high levels of homozygosity, are cell line‐dependent and not always present. PESC lines were derived in high enough yields to be practicable, and their derivatives are suitable for autologous transplantation into oocyte donors or could be used to establish a bank of histocompatible cell lines for a broad spectrum of patients. Disclosure of potential conflicts of interest is found at the end of this article.
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ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1634/stemcells.2007-0869