Heterozygous Embryonic Stem Cell Lines Derived from Nonhuman Primate Parthenotes

¹ Oregon National Primate Research Center, 505 N.W. 185th Avenue, Beaverton, OR, USA
² Whitehead Institute for Biomedical Research; Cambridge Center, Cambridge, MA, USA
³ Veterinary Genetics Laboratory, University of California, Davis, CA, USA
⁴ Oregon National Primate Research Center; Oregon Stem Cell Center and Department of Obstetrics and Gynecology, Oregon Health & Science University, 505 N.W. 185th Avenue, Beaverton, OR, USA

^* To whom correspondence should be addressed. E-mail: mitalipo{at}ohsu.edu.

	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 bi-parental 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 (MHC) region carrying haplotypes identical to 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.