Induced pluripotent stem cells (iPSCs), generated by the overexpression of transcription factors Oct4, Sox2, Klf4 and c‐Myc in somatic cells, are pluripotent. iPSCs reprogrammed from differentiated cells get through a epigenetic modification during reprogramming and finally have the similar epigenetic state to embryonic stem cells (ESCs). In this study, these epigenetic changes were observed in reprogramming of uni‐parental parthenogenetic somatic cells. Furthermore, we have shown that parthenogenetic pattern of imprinted genes were changed during pluripotential reprogramming. Parthenogenetic neural stem cells (pNSCs) containing only maternal alleles regain the biparental imprinting patterns after reprogramming. However, we have yet to define whether the changed imprinted genes are maintained or reverted to the parthenogenetic state when the reprogrammed cells are differentiated into specialized cell types. To address this question, we compared genome‐wide expression profiles of biparental female neural stem cells (fNSCs), parthenogenetic neural stem cells (pNSCs), and NSCs differentiated from parthenogenetic maternal iPSC (miPS‐NSCs). Furthermore, this study establishes the correlation between the alteration of genome methylation and activation of imprinting genes in the parthenogenetic cells and reports for the first time that the silenced PWS‐related imprinted genes are activated in miPS‐NSCs. Our data demonstrated that pluripotential reprogramming of parthenogenetic somatic cells were able to reset the parthenogenetic imprinting patterns; reprogrammed miPSCs showed erasure of maternal methylation imprints and acquisition of methylation in paternally imprinted genes. Furthermore, the changed imprinting patterns were maintained when the reprogrammed cells are differentiated into specialized cell type. * This work was supported by the Next‐Generation BioGreen 21 program (Grant PJ008- 009) funded by the Rural Development Administration, Republic of Korea.

In haplodiploid sex determination, females are sexually reproduced from fertilized diploid eggs, and males from unfertilized haploid eggs. Haplodiploid sex determination seems simple in that sex depends simply on the ploid level. However, the underlying genetic mechanisms are thought to be much more complicated than expected. Among them, a powerful proposed mechanism is genomic imprinting. All epigenetic on-off systems require target genes, unless the systems target histone proteins on chromosomes. For Hymenoptera, a good candidate target gene in terms of sex determination is known either as feminizer (fem) or transformer (tra) in many insects. These two genes are essential for expressing femaleness. In most Hymenopteran insects, the maternal tra seems to be methylated and consequently not expressed, while the paternally derived tra gene is not methylated. Therefore, a fertilized egg with the paternally derived active tra gene will develop into a functional female. Like all Hymenoptera, ants (Formicidae) have haplodiploid sex determination. In Vollenhovia emeryi, however, queens are produced clonally while workers derive from fertilized eggs. Males are haploid, likewise deriving from fertilized eggs, but only after selective elimination of their maternal genome. Under the conventional genomic imprinting model, we would have expected that the opposite pattern of what is observed in others. Here we present extraordinary sex determination and suggest our hypothesis about genomic imprinting pattern in V. emeryi

Haplodiploid sex determination occurs in a wide range of animals, especially in Hymenoptera, where a fertilized egg develops into a diploid female and unfertilized into a haploid male. However, recent studies on diploid functional males in some wasps suggest that the simple addition of paternal gene by fertilization may not be enough to explain female offspring production in the sex determination system. Recently, activation of sex determination gene (tra) was found to have a pivotal role in determining the sex of Nasonia vitripennis. In N. vitripennis, tra is activated only on the paternal genome (i.e. sperm) not on the maternal counterpart (i.e. egg). Such parent specific activation of a gene is controlled by a epigenetic factor, DNA methylation. However, in Trichogramma kaykai, Wolbachia induces female offspring production without sperm. Therefore all female offspring are clonal to the maternal gene. This violates the role of activated sex determination gene (tra) from sperm in the wasp. We hypothesize that Wolbachia has an ability to activate the gene by demethylation. This hypothesis indicates that the target of sex ratio distorting endosymbionts may be an upstream gene. It will enhance our understanding of evolution of haplodiploid sex determination.

Genomic imprinting is defined as parent-of-origin expression of specific genes and may play an important role in embryonal development of mammals. Loss of imprinting(LOI), biallelic expression of the imprinted genes, have been observed in a variety of human tumors and syndromes. H19, a paternally imprinted gene, is transcribed as an untranslated RNA that serves as a riboregulator. LOI of H19 is observed in a variety of human malignancies. In this study, LOI of H19 was examined in head and neck squamous cell carcinomas(HNSCCs). Four(28.6%) of the 14 HNSCCs and 8(28.6%) of the 28 inflammatory oral lesions were informative for imprinting analysis of H19. H19 was imprinted in all inflammatory oral lesions, however, 2(50%) of the 4 informative HNSCCs manifested LOI. These data suggest that LOI of the H19 may play a role in the oncogenesis of HNSCC.