Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 18, Issue 6, Pages 735-U139Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2050
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Funding
- Israel Science Foundation-Morasha Foundation [943/09]
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To study the role of parental imprinting in human embryogenesis, we generated parthenogenetic human induced pluripotent stem cells (iPSCs) with a homozygote diploid karyotype. Global gene expression and DNA methylation analyses of the parthenogenetic cells enabled the identification of the entire repertoire of paternally expressed genes. We thus demonstrated that the gene U5D, encoding a variant of the U5 small RNA component of the spliceosome, is an imprinted gene. Introduction of the U5D gene into parthenogenetic cells partially corrected their molecular phenotype. Our analysis also uncovered multiple miRNAs existing as imprinted clustered transcripts, whose putative targets we then studied further. Examination of the consequences of parthenogenesis on human development identified marked effects on the differentiation of extraembryonic trophectoderm and embryonic liver and muscle tissues. This analysis suggests that distinct regulatory imprinted small RNAs and their targets have substantial roles in human development.
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