Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to ...apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations.
The parent-specific monoallelic expression of imprinted genes is controlled by DNA methylation marks that are established differentially in the germline. Perturbation of these marks leads to loss of ...imprinting (LOI), which is associated with developmental disorders and malignancy and may also obstruct applications of human pluripotent stem cells (hPSCs). Previous studies of LOI in hPSCs were performed on relatively small numbers of cell lines, often leading to conflicting conclusions regarding imprinting stability. Here, we chart the landscape of LOI in hPSCs by applying a large-scale analysis of allele-specific RNA-seq data from more than 270 hPSC samples. We show that reprogrammed hPSCs acquire higher levels of LOI compared with embryonic stem cells and that LOI can pre-exist in their somatic cells of origin. Furthermore, different imprinted genes vary with respect to LOI incidence, surprisingly revealing that those controlled paternally are more prone to disruption. Our findings emphasize the importance of inspecting the imprinting status of hPSCs.
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•Large-scale analysis of loss-of-imprinting (LOI) in human PSCs (hPSCs)•Reprogrammed hPSCs acquire higher levels of LOI compared with embryonic stem cells•Paternally imprinted genes are more prone to LOI•These findings emphasize the importance of inspecting the imprinting status of hPSCs
Bar et al. present a large-scale analysis of loss of imprinting (LOI) in human pluripotent stem cells (hPSCs). They demonstrate differences in LOI abundance between hPSCs depending on their derivation method and between imprinted genes according to their parent of origin. This should be considered in future applications of hPSCs.
A variety of species of bacteria are known to colonize human tumours
, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their ...responses to treatment
. However, it is not known whether antigens derived from intracellular bacteria are presented by the human leukocyte antigen class I and II (HLA-I and HLA-II, respectively) molecules of tumour cells, or whether such antigens elicit a tumour-infiltrating T cell immune response. Here we used 16S rRNA gene sequencing and HLA peptidomics to identify a peptide repertoire derived from intracellular bacteria that was presented on HLA-I and HLA-II molecules in melanoma tumours. Our analysis of 17 melanoma metastases (derived from 9 patients) revealed 248 and 35 unique HLA-I and HLA-II peptides, respectively, that were derived from 41 species of bacteria. We identified recurrent bacterial peptides in tumours from different patients, as well as in different tumours from the same patient. Our study reveals that peptides derived from intracellular bacteria can be presented by tumour cells and elicit immune reactivity, and thus provides insight into a mechanism by which bacteria influence activation of the immune system and responses to therapy.
Abstract This study investigated the effects of religious education on student religious identity over and above parent religiosity by examining student perceptions of two aspects of teacher ...functioning: teacher caring and teacher as role-model. We posited that effects of these variables on students' religious identity are mediated by student perceptions that the school provides a non-alienating religious atmosphere and meaningful religious studies. Participants were 2691 male and female students (grades 9–12) in 152 classes of 25 schools from the Jewish public-religious sector in Israel. Results indicate that in addition to their parents' religiosity, adolescents' perceptions of their teachers as role models and their religious studies as meaningful are important variables affecting their religious identity. Moreover, this research suggests that religious identity formation processes flourish in an educational environment which students perceive as accommodating religious exploration.
The goal of the present study was to assess the similarities and differences between parents from different cultures in terms of the intensity of parental identity processes described in the ...three-dimensional model of identity formation. The cultural measurement invariance of the questionnaire used, the Utrecht-Management of Identity Commitments Scale-Parental Identity (U-MICS-PI), was also assessed. Participants were 2340 parents (51.4% of mothers) aged from 30 to 59 (M = 43.54; SD = 8.26). The study included parents from North America (USA), the Middle East (Israel), Central Europe (Poland), Africa (South Africa), and Eastern Asia (Japan). Results indicated the full configural, partial metric, and partial scalar invariance of the U-MICS-PI. A comparison of parents from the countries analyzed revealed that the parents from the United States and South Africa were characterized by a more firm commitment and lower level of reconsideration of commitment than those from Poland and Japan.
To examine the chromosomal content of embryos resulting from metaphase I (MI) oocytes obtained after ovarian hyperstimulation for IVF.
Prospective cohort study.
University-based IVF Center, Assaf ...Harofeh Medical Center, Tel Aviv University, Israel.
One hundred fifty women undergoing assisted reproduction technique (ART).
Intracytoplasmic sperm injection (ICSI) was performed in MI oocytes that were retrieved after ovarian stimulation. A portion of these oocytes extruded their polar body (rescued in vitro-matured metaphase II IVM-MII) after different incubation periods and the remainder did not (arrested MI oocytes). Fluorescence in situ hybridization was performed using probes for chromosomes X, Y, 18.
Fertilization rate, number of blastomeres, and embryo euploidy.
Embryos from rescued IVM-MII oocytes showed significantly higher fertilization rates and more blastomeres per embryo compared with those from arrested MI oocytes (58.5% vs. 43.9% and 5.7 vs. 5.0, respectively). The chromosomal analysis of these embryos revealed a high rate of aberrations (80.6%), mainly complex mosaics. This rate was elevated in embryos from arrested IVM oocytes (97.2%), and after longer incubation periods. No chromosomally normal embryos were found after 24 hours of incubation of their corresponding oocytes.
Embryos originating from MI oocytes have a high rate of chromosomal aneuploidy, and their replacement should be reconsidered.
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