Discovery of a novel imprinted gene by transcriptional analysis of parthenogenetic embryonic stem cells

Hathaitip Sritanaudomchai, Hong Ma, Lisa Clepper, Sumita Gokhale, Randy Bogan, Jon Hennebold, Don Wolf, Shoukhrat Mitalipov

    Research output: Contribution to journalArticlepeer-review

    25 Scopus citations

    Abstract

    Background: Parthenogenetic embryonic stem cells (PESCs) may have future utilities in cell replacement therapies since they are closely related to the female from which the activated oocyte was obtained. Furthermore, the avoidance of parthenogenetic development in mammals provides the most compelling rationale for the evolution of genomic imprinting, and the biological process of parthenogenesis raises complex issues regarding differential gene expression. Methods: AND Results: We describe here homozygous rhesus monkey PESCs derived from a spontaneously duplicated, haploid oocyte genome. Since the effect of homozygosity on PESCs pluripotency and differentiation potential is unknown, we assessed the similarities and differences in pluripotency markers and developmental potential by in vitro and in vivo differentiation of homozygous and heterozygous PESCs. To understand the differences in gene expression regulation between parthenogenetic and biparental embryonic stem cells (ESCs), we conducted microarray analysis of genome-wide mRNA profiles of primate PESCs and ESCs derived from fertilized embryos using the Affymetrix Rhesus Macaque Genome array. Several known paternally imprinted genes were in the highly down-regulated group in PESCs compared with ESCs. Furthermore, allele-specific expression analysis of other genes whose expression is also down-regulated in PESCs, led to the identification of one novel imprinted gene, inositol polyphosphate-5-phosphatase F (INPP5F), which was exclusively expressed from a paternal allele. Conclusion: Our findings suggest that PESCs could be used as a model for studying genomic imprinting, and in the discovery of novel imprinted genes.

    Original languageEnglish (US)
    Pages (from-to)1927-1941
    Number of pages15
    JournalHuman Reproduction
    Volume25
    Issue number8
    DOIs
    StatePublished - Aug 2010

    Keywords

    • homozygosity
    • imprinting
    • parthenogenesis
    • pluripotent stem cells

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology

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