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Aims/hypothesis: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected 'hub' cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. Methods: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. Results: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. 'Hub' cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. Conclusions/interpretation: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. Data availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465. [ABSTRACT FROM AUTHOR]

The productivity of beef cows depends on early reproduction traits such as puberty and has an economic impact on the efficiency of production system. Imprinted genes modulate many important endocrine processes such as growth, the onset of puberty and maternal reproductive and behavior. The role of imprinted genes in puberty is a challenging subject since they show the reciprocal role of maternal and paternal genomes in progeny. Although, there are evidences of the involvement of imprint genes in puberty in human, the role of this type of genes in the onset of puberty in cattle has not been studied yet. Here we examined the expression of 27 imprinted genes in pre and post puberty in a bovine model to find differentially expressed imprinted genes in maternal-paternal purebreds and reciprocal crosses across eight tissues and discussed the task of these genes in this crucial process of development and in onset of puberty. DLK1 and MKRN3 that previously described as cause of the central precocious puberty (CPP) in human were differentially expressed in this study. Functional annotation analysis of differentially imprinted genes in different tissues showed significant biological processes of cellular response to growth factor stimulus, response to growth factor, response to parathyroid hormone, developmental growth and the importance of alternative splicing. The results of this study have implications in understanding the role of imprinted genes in the onset of puberty in cattle. [ABSTRACT FROM AUTHOR]

Immature teratomas are a subset of ovarian teratomas, and the pathogenic relationship between mature and immature ovarian teratomas is unclear. Mature ovarian teratomas are parthenogenetic tumors that arise from a single oocyte/ovum, whereas the origin of immature ovarian teratomas has not been extensively investigated. Since parthenogenetic tumors contain only maternal genomes, genome imprinting in these tumors usually follows a maternal pattern. DNA methylation is among the most important mechanisms of genome imprinting. Therefore, we analyzed the methylation profile of imprinted genes by performing methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of 25 imprinting control regions (ICRs) in 10 imprinted genes/gene clusters from formalin-fixed, paraffin-embedded samples obtained from 4 immature ovarian teratomas, 8 mature ovarian teratomas, and 4 ovarian yolk sac tumors (YSTs). Both the immature and mature components showed similar methylation levels in each ICR in immature teratomas. Overall, immature ovarian teratomas showed maternal methylation patterns of imprinted genes in concordance with their parthenogenetic origin. However, they also showed aberrant methylation levels in a few imprinted genes, suggesting that genome imprinting in immature teratomas may partially differ from that in mature teratomas. Microscopic foci of YST were seen in one immature teratoma; the YST component also showed a maternal methylation pattern, unlike the pure YSTs that showed irregular patterns. Thus, teratoma-associated YST and pure YST may have different pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Oocyte vitrification is an important assisted reproductive technology (ART) that preserves the fertility of unmarried patients with malignant tumors, and promotes the development of the oocyte donation program. In recent years, the effects of ART, including the vitrification of oocytes and embryos on the health of offspring, have attracted much attention; however, it is difficult to conduct long-term follow-up and biochemical evaluation in humans. In this study, we detected the effect of oocyte vitrification on gene expression in the organs of adult mice offspring by RNA sequencing for the first time. Our results showed that only a small amount of gene expression was significantly affected. Seven genes (Tpm3, Hspe1-rs1, Ntrk2, Cyp4a31, Asic5, Cyp4a14, Retsat) were abnormally expressed in the liver, and ten genes (Lbp, Hspe1-rs1, Prxl2b, Pfn3, Gm9008, Bglap3, Col8a1, Hmgcr, Ero1lb, Ifi44l) were abnormal in the kidney. Several genes were related to metabolism and disease occurrence in the liver or kidney. Besides, we paid special attention to the expression of known imprinted genes and DNA methylation–related genes in adult organs, which are susceptible to oocyte cryopreservation in the preimplantation stage. As a result, some of these transcripts were detected in adult organs, but they were not affected by oocyte vitrification. In conclusion, we first report that oocyte vitrification did not significantly change the global gene expression in offspring organs; nonetheless, it can still influence the transcription of a few functional genes. The potential adverse effects caused by oocyte vitrification need attention and further study. [ABSTRACT FROM AUTHOR]

Purpose: Changes in DNA methylation modifications have been associated with male infertility. With the development of assisted reproductive technologies (ARTs), abnormal DNA methylation in sperm, especially in imprinted genes, may impact the health of offspring and requires an in-depth study. Methods: In this study, we collected abnormal human semen samples, including asthenospermic, oligospermic, oligoasthenospermic and deformed sperm, and investigated the methylation of imprinted genes by reduced representation bisulfite sequencing (RRBS) and bisulfite amplicon sequencing on the Illumina platform. Results: The differentially methylated regions (DMRs) of imprinted genes, including H19, GNAS, MEG8 and SNRPN, were different in the abnormal semen groups. MEG8 DMR methylation in the asthenospermic group was significantly increased. Furthermore, higher methylation levels of MEG8, GNAS and SNRPN DMR in the oligospermic and oligoasthenospermic groups and a decrease in the H19 DMR methylation level in the oligospermic group were observed. However, the methylation levels of these regions varied greatly among the different semen samples and among individual sperm within the same semen sample. The SNP rs2525883 genotype in the H19 DMR affected DNA methylation. Moreover, DNA methylation levels differed in the abnormal semen groups in the non-imprinted genomic regions, including repetitive sequence DNA transposons and long/short interspersed nuclear elements (LINEs and SINEs). Conclusion: Our study established that imprinted gene DMRs, such as H19, GNAS, SNRPN and MEG8, were differentially methylated in the abnormal semen groups with obvious inter- and intra-sample heterogeneities. These results suggest that special attention needs to be paid to possible epigenetic risks during reproduction. [ABSTRACT FROM AUTHOR]

TET enzymes oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), a process thought to be intermediary in an active DNA demethylation mechanism. Notably, 5hmC is highly abundant in the brain and in neuronal cells. Here, we interrogated the function of Tet3 in neural precursor cells (NPCs), using a stable and inducible knockdown system and an in vitro neural differentiation protocol. We show that Tet3 is upregulated during neural differentiation, whereas Tet1 is downregulated. Surprisingly, Tet3 knockdown led to a de-repression of pluripotency-associated genes such as Oct4, Nanog or Tcl1, with concomitant hypomethylation. Moreover, in Tet3 knockdown NPCs, we observed the appearance of OCT4-positive cells forming cellular aggregates, suggesting de-differentiation of the cells. Notably, Tet3 KD led to a genome-scale loss of DNA methylation and hypermethylation of a smaller number of CpGs that are located at neurogenesis-related genes and at imprinting control regions (ICRs) of Peg10, Zrsr1 and Mcts2 imprinted genes. Overall, our results suggest that TET3 is necessary to maintain silencing of pluripotency genes and consequently neural stem cell identity, possibly through regulation of DNA methylation levels in neural precursor cells. [ABSTRACT FROM AUTHOR]

Non-mendelian inheritance refers to the group of phenomena and observations related to the inheritance of genetic information that cannot be merely explained by Mendel’s laws of inheritance. Phenomenon including Genomic imprinting, X-chromosome Inactivation, Paramutations are some of the best studied examples of non-mendelian inheritance. Genomic imprinting is a process that reversibly marks one of the two homologous loci, chromosome or chromosomal sets during development, resulting in functional non-equivalence of gene expression. Genomic imprinting is known to occur in a few insect species, plants, and placental mammals. Over the years, studies on imprinted genes have contributed immensely to highlighting the role of epigenetic modifications and the epigenetic circuitry during gene expression and development. In this review, we discuss the phenomenon of genomic imprinting in mammals and the role it plays especially during fetoplacental growth and early development. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been widely found in the environment. The chemical 2,3′,4,4′5-pentachlorobiphenyl (PCB118) is an important dioxin-like PCB compound with strong toxicity. PCB118 can accumulate in adipose tissue, serum and milk in mammals, and it is highly enriched in the follicular fluid. In this study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during pregnancy at the fetal primordial germ cell migration stage. The methylation patterns of the imprinted genes H19, Snrpn, Peg3 and Igf2r as well as the expression levels of Dnmt1, 3a, 3b and 3l, Uhrf1, Tet2 and Tet3 in fully grown germinal vesicle oocytes were measured in offspring. The rates of in vitro maturation, in vitro fertilization, oocyte spindle and chromosomal abnormalities were also calculated. The results showed that prenatal exposure to PCB118 altered the DNA methylation status of differentially methylated regions in some imprinted genes, and the expression levels of Dnmt1, 3a, and 3l, Uhrf1 and Tet3 were also changed. In addition, PCB118 disturbed the maturation process of progeny mouse oocytes in a dose-dependent manner. Therefore, attention should be paid to the potential impacts of PCB118-contaminated dietary intake during pregnancy on the offspring's reproductive health. [ABSTRACT FROM AUTHOR]

Purpose: Despite the growing body of research implying an impact of in vitro fertilization (IVF) on imprinted genes and epigenetics, few studies have examined the effects of underlying subfertility or prenatal stress on epigenetics, particularly in terms of their role in determining infant birthweights. Both subfertility and prenatal stressors have been found to impact epigenetics and may be confounding the effect of IVF on epigenetics and imprinted genes. Like IVF, both of these exposures—infertility and prenatal stressors—have been associated with lower infant birthweights. The placenta, and specifically epigenetically regulated placental imprinted genes, provides an ideal but understudied mechanism for evaluating the relationship between underlying genetics, environmental exposures, and birthweight. Methods and results: In this review, we discuss the impacts of IVF and infertility on birthweight, epigenetic mechanisms and genomic imprinting, and the role of these mechanisms in the IVF population and discuss the role and importance of the placenta in infant development. We then highlight recent work on the relationships between infertility, IVF, and prenatal stressors in terms of placental imprinting. Conclusions: In combination, the studies discussed, as well as two recent projects of our own on placental imprinted gene expression, suggest that lower birthweights in IVF infants are secondary to a combination of exposures including the infertility and prenatal stress that couples undergoing IVF are experiencing. The work highlighted herein emphasizes the need for appropriate control populations that take infertility into account and also for consideration of prenatal psychosocial stressors as confounders and causes of variation in IVF infant outcomes. [ABSTRACT FROM AUTHOR]

Given the higher risk of developing imprinting disorders in assisted reproductive technology (ART)-conceived children, we hypothesized that ART may affect DNA methylation of the insulin-like growth factor 2 (IGF2), H19, small nuclear ribonucleoprotein polypeptide N (SNRPN) differentially methylated regions (DMRs) at the fetal stage, which in turn may be associated with sperm abnormalities. A total of 4 patient groups were recruited, namely, multifetal reduction following in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI; n = 56), multifetal reduction following controlled ovarian hyperstimulation (COH; n = 42), male patients with normal semen parameters denoted as normozoospermia group (NZ) for IVF (n = 36), and male patients presenting with asthenozoospermia (OAZ) for ICSI (n = 38). The expression levels and the DNA methylation status of IGF2 - H19 and SNRPN DMRs in the fetuses and the semen samples were evaluated by real-time quantitative polymerase chain reaction and pyrosequencing. In our results, the expression levels of H19 were significantly higher, whereas the methylation rates were lower in IVF-conceived fetuses compared to the control group (P <.05). Furthermore, higher methylation rates of IGF2 DMR2 and SNRPN DMR were detected both in IVF- and ICSI-conceived fetuses (P <.05). The data further indicated that the patients who presented with the majority of the CpG sites in the H19 DMR region that were lower methylated were those in the OAZ group. The results demonstrated that the epigenetic dysregulations of IGF2-H19 and SNRPN DMRs that were caused by ART were noted in the fetuses. Moreover, the present study suggested that epigenetic perturbations of the H19 DMR might be a key biomarker for spermatogenesis defects in humans. [ABSTRACT FROM AUTHOR]

Imprinted gene expression in flowering plants predominantly occurs in the triploid endosperm of developing seed. However, endosperm is composed of distinct tissue types. For example, the maize ( Zea mays) endosperm is constituted by two major tissues, starchy endosperm and aleurone. Previous studies in imprinted gene expression have generally assumed that the different tissues constituting endosperm would behavior the same, and hence have not examined them separately. Here, to examine parental-specific expression of imprinted genes in different parts of the seed, eight previously reported maize protein-coding imprinted genes were selected, and analyzed by cleaved amplified polymorphic sequence (CAPS) coupled with Sanger sequencing for transcripts from the various seed tissues collected at 18 days after pollination (DAP). The studied tissues included seed coat, embryo, starchy endosperm and aleurone, which were collected from a pair of reciprocal F1 hybrids produced by crossing inbred lines B73 and Mo17. Six of these eight analyzed imprinted genes showed the same imprinted expression pattern between the starchy endosperm and aleurone, but two showed imprinted expression only in the starchy endosperm. Comparison of the expression pattern of 20 selected imprinted genes in multiple seed tissues and vegetative tissues indicated that the majority (~ 75%) of these imprinted genes exhibited seed-specific or endosperm-specific expression. Our results also uncovered that imprinted genes have a high propensity to be alternatively spliced via intron retention in the developing embryo compared with the other tissues. [ABSTRACT FROM AUTHOR]

Increasing numbers of reports show that imprinted genes play a crucial role in fetal development, and uniparental embryos, which possess two paternally or two maternally derived pronuclei, are excellent tools for investigating the biological significance of imprinted genes. In the present study, to examine the in vitro developmental ability and expression pattern of eight imprinted genes in uniparental embryos, we produced androgenones, gynogenones, and parthenogenones using enucleation. Our data confirmed the previously observed restriction in haploid androgenetic development potential and first indicated that diploid androgenetic embryos were arrested in the 3/4-cell stage. Some imprinted genes were expressed in androgenetic, gynogenetic, and parthenogenetic blastocysts, suggesting that they were unable to maintain their imprinted expression status in uniparental embryos and that both paternal and maternal alleles are required for the specific expression of some imprinted genes. [ABSTRACT FROM AUTHOR]

Purpose: To study the relationship of imprinted gene expression ( CDKN1C, H19, IGF2, KCNQ1 and PHLDA2) with human fetal growth. Methods: RNA was extracted from fetuses with intrauterine growth restriction (IUGR) and from the controls without growth restriction. The gene expression pattern of CDKN1C, H19, IGF2, KCNQ1 and PHLDA2 genes was evaluated using RT-PCR. MS-MLPA was also performed to assess the IC1 and IC2 DNA methylation status on chromosome 11p15.5. Results: The samples were divided according to their tissue type in placental or fetal tissue. Within each group, IUGR cases and controls were compared. In the IUGR cases, in both fetal and placental tissue groups IGF2 was observed to be down regulated. In another approach, the samples were divided in IUGR and control groups and for each of them placental and fetal tissue was compared. Within the IUGR group up regulation of CDKN1C, KCNQ1, and PHLDA2 was determined in placental samples. IUGR group presented a statistically lower methylation status in both IC1 and in IC2. Regarding differences between fetal and placental samples within this group, methylation status of placental samples was statistically significant down regulated in the imprinting center 1 (IC1). Conclusions: Genomic imprinting is a phenomenon that plays an important role in fetal and placental development. This study emphasizes the importance of imprinted genes during pregnancy. Differences between tissues could reflect different mechanisms, either compensatory or adverse, that should be investigated in more detail. [ABSTRACT FROM AUTHOR]

Genomic imprinting is an epigenetic state that results from differential processing of chromosomes during gametogenesis and which can cause differential expression of genes depending on the sex of the parent transmitting that gene. In Drosophila, many examples of imprinted marker genes have been documented and imprinting of these genes involves highly conserved epigenetic regulators. However, no endogenously imprinted genes have yet been identified. Here we present a phenotypic and transcriptional analysis of parthenogenetic (gynogenetic) and genotypically identical but sexually produced adult female Drosophila. We find that while parthenogenetic females have a superficially normal phenotype and are viable and fertile, their lifespan is extended relative to their sexually-produced counterparts. Microarray/transcriptional analysis of parthenogenetic versus sexually-produced females reveals 76 genes with consistently altered patterns of expression, 36 upregulated and 40 downregulated, some with known effects on aging. Analysis of individuals with uniparental inheritance of only portions of their genome suggest that many of these genes may be indirectly imprinted, responding to either other imprinted genes or redistribution of chromatin components that are differentially allocated to sex and autosomal heterochromatin in a sex-dependent manner during gametogenesis. As gene expression dependent on the parental origin of the genome meets the definition of genomic imprinting, our study provides evidence that endogenous genes are imprinted in Drosophila. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE: We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT). METHODS: We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ≥30 kgm−2, was ascertained through standardized questionnaires. RESULTS: After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β = −2.57; s.e.=0.95; P=0.008), PEG3 (β = −1.71; s.e.=0.61; P=0.005) and NNAT (β = −3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β -coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and −3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR. CONCLUSION: We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring’s methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood. [ABSTRACT FROM AUTHOR]

In mammals, the somatic growth rate is rapid during fetal and early postnatal life and then gradually declines and eventually stops. In search of the fundamental biological mechanism causing coordinated growth deceleration in multiple tissues, a network of imprinted genes was recently identified based on a coordinated decline in expression in several organs during postnatal growth. To explore a possible role in longitudinal bone growth, we characterized expression of the network during postnatal growth in microdissected metaphyseal bone and growth plate zones of 1-, 3-, and 9-week-old rats using real-time PCR. The expression pattern of the network is modified in growth plate. Similar to the coordinated decline previously observed in kidney, lung, liver, and heart, expression of all genes, except Gtl2, decreased with age in metaphyseal bone. On the contrary, Mest, Dlk1, H19, and Gtl2 decreased, and Cdkn1c, Grb10, and Slc38a4 increased with age in growth plate. During differentiation from resting to hypertrophic zone, Mest, Dlk1, Grb10, and Gtl2 expression decreased, whereas Slc38a4 expression increased. In particular, developmental changes in the expression of growth-promoting genes, Mest, Dlk1, Gtl2, and growth-inhibitory genes, Cdkn1c and Grb10, may contribute to the decline in longitudinal bone growth that occurs with age. [ABSTRACT FROM AUTHOR]

Objective:Due to the extensive use of intracytoplasmic sperm injection (ICSI) in assisted reproduction, not only among couples with severe male factor infertility problems, but to a broader scale, a lot of concern has been raised regarding the safety of the method and its implications in epigenic control and imprinting dysregulation. This review means to provide a comprehensive report of the published scientific data, outline putative associations between ICSI and epigenetic control,and suggest measures to improve the current state of affairs and reach more scientifically consolidated results.Methods:This review was conducted by studying a broad spectrum of articles dealing with the subject of epigenetic control and its relation with ICSI. We tried to view the two subjects as parallel procedures that occur in the organism and by delineating the molecular and biochemical steps that comprise them make suggestions about putative associations between ICSI and epigenetic control.Conclusions:No hard evidence presented at the moment can prove or disapprove ICSI's implications in epigenetic control. Nevertheless, we take the view that more comprehensive, long-term, and properly designed studies are imperative to be applied on a large-scale basis. We urge cautiousness, since the welfare of our progeny is what is at stake. [ABSTRACT FROM PUBLISHER]

Expression of imprinted genes is dependent on their parental origin. This is reflected in the heritable differential methylation of parental alleles. The gametic imprints are however reversible as they do not endure for more than one generation. To investigate if the epigenetic changes in male and female germ line are similar or not, we derived embryonic germ (EG) cells from primordial germ cells (PGCs) of day 11.5 and 12.5 male and female embryos. The results demonstrate that they have an equivalent epigenotype. First, chimeras made with EG cells derived from both male and female embryos showed comparable fetal overgrowth and skeletal abnormalities, which are similar to but less severe than those induced by androgenetic embryonic stem (ES) cells. Thus, EG cells derived from female embryos resemble androgenetic ES cells more than parthenogenetic cells. Furthermore, the methylation status of both alleles of a number of loci in EG cells was similar to that of the paternal allele in normal somatic cells. Hence, both alleles of Igf2r region 2, Peg1/Mest, Peg3, Nnat were consistently unmethylated in EG cells as well as in the primary embryonic fibroblasts (PEFs) rescued from chimeras. More strikingly, both alleles of p57kip2 that were also unmethylated in EG cells, underwent de novo methylation in PEFs to resemble a paternal allele in somatic cells. The exceptions were the H19 and Igf2 genes that retained the methylation pattern in PEFs as seen in normal somatic tissues. These studies suggest that the initial epigenetic changes in germ cells of male and female embryos are similar. [ABSTRACT FROM AUTHOR]

Human parthenogenetic embryonic stem cells (pESCs) were previously thought to be better cell sources for ESC banking because the homozygous Human Leukocyte Antigen (HLA) would strongly increase the matching degree for certain population with relatively smaller cohorts of cell lines. While recent studies have shown that upon currently used strategy to artificial activate oocyte without second polar body extrusion, most pESCs derived would be predominantly heterozygous due to early recombination events in oocyte. Here we reported successful derivation of human homozygous and heterozygous pESC lines from one pronuclear zygote following routine in vitro fertilization treatment and artificial parthenoactivation. The hESC characters, SNPs genotyping, gene expression profiles were conducted and compared to other normal hESCs. The in vitro differentiation ability and the epigenetic stability of imprinted genes of these two cell lines before and post differentiation were further evaluated. [ABSTRACT FROM AUTHOR]