TY - JOUR
T1 - Discovery of a novel imprinted gene by transcriptional analysis of parthenogenetic embryonic stem cells
AU - Sritanaudomchai, Hathaitip
AU - Ma, Hong
AU - Clepper, Lisa
AU - Gokhale, Sumita
AU - Bogan, Randy
AU - Hennebold, Jon
AU - Wolf, Don
AU - Mitalipov, Shoukhrat
N1 - Funding Information:
This work was supported by start up funds from Oregon National Primate Research Center, Oregon Stem Cell Center and grants from the Stem Cell Research Foundation and the National Institutes of Health HD057121, HD059946, HD063276, RR000163, HD047675, HD018185 and HD047721.
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - homozygosity
KW - imprinting
KW - parthenogenesis
KW - pluripotent stem cells
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U2 - 10.1093/humrep/deq144
DO - 10.1093/humrep/deq144
M3 - Article
C2 - 20522441
AN - SCOPUS:77954983860
SN - 0268-1161
VL - 25
SP - 1927
EP - 1941
JO - Human Reproduction
JF - Human Reproduction
IS - 8
ER -