Heterozygous embryonic stem cell lines derived from nonhuman primate parthenotes

Vikas Dighe, Lisa Clepper, Darlene Pedersen, James Byrne, Betsy Ferguson, Sumita Gokhale, Cecilia Penedo, Don Wolf, Shoukhrat Mitalipov

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)756-766
Number of pages11
JournalStem Cells
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Embryonic stem cells
  • Histocompatible
  • Imprinting
  • Meiotic recombination
  • Parthenogenetic

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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