Global analysis of parental imprinting in human parthenogenetic induced pluripotent stem cells

Yonatan Stelzer, Ofra Yanuka, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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.

Original languageAmerican English
Pages (from-to)735-741
Number of pages7
JournalNature Structural and Molecular Biology
Issue number6
StatePublished - Jun 2011

Bibliographical note

Funding Information:
We thank M. Pick for her help with generating parthenogenetic iPSCs and O. Bar-Nur for providing WT-HiPSCs; U. Ben-David for his technical help with the teratoma formation experiments; T. Golan-Lev for her assistance with the graphic design and immunostaining assays; and A. Eden, D. Kitsberg, Y. Mayshar, D. Ronen and N. Sharon for critical reading of the manuscript. N.B. is the Herbert Cohn Chair in Cancer Research. This research was supported partially by the Israel Science Foundation–Morasha Foundation (grant no. 943/09).


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