A survey of imprinted gene expression in mouse trophoblast stem cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE63968 | GEO | 2015/02/24
SECONDARY ACCESSION(S): PRJNA269732
REPOSITORIES: GEO
Similar Datasets
Project description:Several hundred mammalian genes are expressed preferentially from one parental allele due to a process called genomic imprinting. Genomic imprinting is particularly prevalent in extra-embryonic tissue, where it plays an essential role during development. Here, we profiled imprinted gene expression via RNA-Seq in a panel of six mouse trophoblast stem (TSC) lines, which are ex vivo derivatives of a progenitor population that gives rise to the placental tissue of the mouse. We found evidence of imprinted expression for 48 genes, 31 of which had previously been described as imprinted and 17 of which we suggest as candidate imprinted genes. An equal number of maternally and paternally biased genes were detected. Several genes showed variability in imprinted expression between the six TSC lines. Sixteen of the 48 known and candidate imprinted genes were previously or newly annotated noncoding RNAs, and six encoded for a total of 60 annotated microRNAs. Pyrosequencing across a panel of six TSC lines returned levels of imprinted expression that were concordant with RNA-Seq measurements for eight genes examined in all six independently derived TSC lines. Our results solidify TSCs as a cell culture-based experimental model to study genomic imprinting, and provide a quantitative foundation upon which to delineate mechanisms by which the process is maintained in the mouse. RNA-Seq from F1 hybrid TSC lines generated from crosses between Cast and B6 mice.
2015-02-24 | E-GEOD-63968 | biostudies-arrayexpress
Project description:The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes of which 10 were paternally expressed. An additional 78 candidate novel imprinted genes identified by RNA-seq also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the novel genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase (HAT1), the first example of an imprinted gene involved in chromatin modification, and LY6G6C, the first imprinted gene to be identified in the major histocompatibility complex. The 78 novel candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting. Examine allelic expression from four individual samples of invasive trophoblast tissue of the chorionic girdle from gestation day 33 conceptuses of horse, donkey, mule and hinny.
2013-05-24 | E-GEOD-30243 | biostudies-arrayexpress
Project description:To identify genomic imprinting in pigs, we generated parthenogenetic porcine embryos alongside biparental normal embryos, and then performed whole-genome bisulfite sequencing and RNA sequencing on these samples. In our analyses, we discovered a maternally methylated differentially methylated region within the orthologous ZNF791 locus in pigs, while identifying both a major imprinted isoform of the ZNF791-like gene and an imprinted antisense transcript that has not been previously annotated. Importantly, our comparative analyses of the orthologous ZNF791 gene in various eutherian mammals, including humans, non-human primates, rodents, artiodactyls, and dogs, revealed that this gene is subjected to genomic imprinting exclusively in domesticated animals, thereby highlighting lineage-specific imprinting.
2024-10-16 | GSE263494 | GEO
Project description:To identify genomic imprinting in pigs, we generated parthenogenetic porcine embryos alongside biparental normal embryos, and then performed whole-genome bisulfite sequencing and RNA sequencing on these samples. In our analyses, we discovered a maternally methylated differentially methylated region within the orthologous ZNF791 locus in pigs, while identifying both a major imprinted isoform of the ZNF791-like gene and an imprinted antisense transcript that has not been previously annotated. Importantly, our comparative analyses of the orthologous ZNF791 gene in various eutherian mammals, including humans, non-human primates, rodents, artiodactyls, and dogs, revealed that this gene is subjected to genomic imprinting exclusively in domesticated animals, thereby highlighting lineage-specific imprinting.
2024-10-16 | GSE263495 | GEO
Project description:The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes of which 10 were paternally expressed. An additional 78 candidate novel imprinted genes identified by RNA-seq also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the novel genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase (HAT1), the first example of an imprinted gene involved in chromatin modification, and LY6G6C, the first imprinted gene to be identified in the major histocompatibility complex. The 78 novel candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting.
2013-05-24 | GSE30243 | GEO
Project description:Background: Genomic imprinting is an epigenetic phenomenon of differential allelic expression based on parental origin. To date a total of 255 imprinted genes have been identified or predicted among all investigated mammal species. However, only 21 have been described in sheep and 11 are annotated in current ovine genome. Results: Here we aim to use DNA/RNA throughput sequencing to identify monoallelically expressed and imprinted genes in organs of day 135 fetal sheep, and 2) to determine whether different levels of maternal energy intake (100% of NRC energy requirement or control, 140% or over-, and 60% or under-fed) influence genomic imprinting. We report strategies to solve technical challenges in the next-generation sequencing data analysis pipeline, including alignment bias of RNA sequencing reads and filtering potential false positives. We identified 80 monoallelically expressed and 18 putatively imprinted genes using the list of 255 stated above as a guide. Five (45.6% of 11) were already known imprinted genes in sheep, the other 13 were known imprinted in other mammals. Sanger sequencing confirmed four putative sheep imprinted genes INPP5F, PLAGL1, CASD1 and PPP1R9A. Among the 13 putative imprinted genes, five localized in the known sheep imprinting clusters of MEST domain on chromosome 4, DLK1/GTL2 domain on chromosome 18 and IGF2/H19 domain on chromosome 21, three were in a novel sheep imprinted cluster on chromosome 4 known in other species as PEG10/SGCE. Additionally, we found that the imprinted genes PHLDA2, SLC22A18, DIRAS3, and IGF2 were differentially expressed, albeit without allelic expression reversal, among the three maternal nutritional groups. Conclusions: Together, our results expanded the sheep imprinted gene list to 34 and demonstrated the influence of maternal diet on fetal imprinting under the conditions studied.
2018-08-29 | GSE111306 | GEO
Project description:Genomic imprinting, resulting in parent-of-origin specific gene expression, plays a critical role in mammalian development. Here, we perform allele-specific RNA-Seq on isogenic B6D2F1 mice to assay imprinted genes in tissues from early embryonic stages and in pluripotent cell lines. For the cell lines, we include embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) derived from fertilized embryos or from embryos obtained after nuclear transfer (NT), as well as B6D2F1 ESCs and EpiSCs derived after parthenogenetic activation (PGA). Notably, the PGA-derived cell lines contain a mosaic genotype due to genomic recombination occurring in the parental B6D2F1 oocyte during meiosis. As the homozygous genomic regions of the PGA-derived cells are not compatible with allele-specific RNA-Seq, we developed an RNA-Seq based genotyping strategy that allows identification of the informative heterozygous regions. Global imprinting analysis shows that ESC lines largely lose imprints as compared to their corresponding embryonic tissues. Fertilized EpiSC and EpiSC-NT lines generally maintain imprinted gene expression. However, two EpiSC-NT lines show aberrant silencing of Rian and Meg3, two critically imprinted genes in mouse iPSCs. EpiSC-PGA lines display loss of imprinting, with known paternally-expressed genes being silenced and known maternally-expressed genes consistently showing doubled expression. Interestingly, most female EpiSC lines show monoallelic expression of Xist and full skewing of X inactivation, suggesting a (near) clonal origin. Together, our analysis provides a comprehensive overview of imprinted gene expression in pluripotency and provides a benchmark to allow identification of cell lines that faithfully maintain imprinted gene expression and therefore retain full developmental potential.
2019-02-16 | GSE101292 | GEO
Project description:The embryo is responsible for transmitting genetic information to the next generation. However, the underlying gene expression and gene imprinting during early embryo development remain largely elusive in maize. Using high-throughput RNA sequencing, we analyzed the allelic gene expression patterns of maize embryos from reciprocal crosses between inbred lines B73 and Mo17 at six time points (3 to 13 days after pollination). A total of 9532 genes were found to be differentially expressed in developmental stage, 3512 of 9532 genes were affected by cross direction. Co-expression analysis uncovered the sequential gene activations during maize embryo development. Further, we found 64 embryo strongly imprinted genes, including 57 maternally expressed imprinted genes (MEG) and 7 paternally expressed imprinted genes (PEG) in the maize embryo. Among them, 20 genes were continuously imprinted and 36 imprinted genes were newly identified. By applying In situ hybridization, we verified that six of the differentially expressed genes showed enriched transcription in the embryo. In addition, mutant analyses indicated that three of the imprinted genes displayed reduced embryo size. Therefore, our data shed new light on our understanding of the gene expression and gene imprinting in early maize embryo development, and suggested that imprinted genes are important for proper embryo development.
2017-12-05 | GSE95399 | GEO
Project description:Genomic imprinting is an allele-specific gene expression system important for mammalian development and function. The molecular basis of genomic imprinting is allele-specific DNA methylation 2. While it is well known that the de novo DNA methyltransferases Dnmt3a/b are responsible for the establishment of genomic imprinting, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains a mystery. Here we report that Tet1 plays a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1-KO males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal functional loss of Tet1. Genome-wide DNA methylation analysis of E13.5 PGCs and sperm derived from Tet1-KO mice reveals hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Dynamics of methylation change in Tet1-affected sites suggested that Tet1 swipes remaining methylation including imprinted genes at late reprogramming stage. We also revealed that Tet1play a role in paternal imprinting erasure in females germline. Thus, our study establishes a critical function for Tet1 in the erasure of genomic imprinting. Genome-wide DNA methylation analysis of E13.5 PGCs from control and Tet1-KO mice
2013-12-02 | E-GEOD-49762 | biostudies-arrayexpress
Project description:Genomic imprinting is an allele-specific gene expression system important for mammalian development and function. The molecular basis of genomic imprinting is allele-specific DNA methylation 2. While it is well known that the de novo DNA methyltransferases Dnmt3a/b are responsible for the establishment of genomic imprinting, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains a mystery. Here we report that Tet1 plays a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1-KO males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal functional loss of Tet1. Genome-wide DNA methylation analysis of E13.5 PGCs and sperm derived from Tet1-KO mice reveals hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Dynamics of methylation change in Tet1-affected sites suggested that Tet1 swipes remaining methylation including imprinted genes at late reprogramming stage. We also revealed that Tet1play a role in paternal imprinting erasure in females germline. Thus, our study establishes a critical function for Tet1 in the erasure of genomic imprinting. Genome-wide DNA methylation analysis of sperm derived from control and Tet1-KO mice
2013-12-02 | E-GEOD-49763 | biostudies-arrayexpress