Imprinted expression is different in visceral yolk sac and cystic embryoid body endoderm
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56276 | GEO | 2015/07/22
SECONDARY ACCESSION(S): PRJNA242816
REPOSITORIES: GEO
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Project description:Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin mono-allelic expression of a small subset of mammalian genes. Imprinted genes have been categorized into two groups: multi lineage (ML) imprinted genes that can show imprinted expression in both embryonic and extra-embryonic lineages, and genes that show extra-embryonic lineage (EXEL) specific imprinted expression restricted to tissues like the placenta and visceral yolk sac (VYS) endoderm. Many genes showing EXEL imprinted expression are silenced by lncRNAs that act over long distances. Thus the analysis of this form of gene silencing is likely to be pivotal for understanding new mechanisms of long range gene silencing by lncRNAs. It has been reported that ES cells differentiated into cystic embryoid bodies (cystic EBs) contain VYS endoderm and here we investigate if cystic EBs could serve as an in vitro model for the analysis of EXEL imprinted expression. Unexpectedly we found that cystic EBs lack EXEL imprinted expression, while retaining normal imprinted expression of ML genes. This shows that cystic EBs do not model VYS imprinted expression and also argues against previous claims that cystic EBs contain VYS endoderm. We further characterized cystic EBs by performing RNA-seq and whole genome bisulphite sequencing. By comparison to various embryonic tissues we found that cystic EBs more resemble embryonic liver, which contains definitive endoderm, than the extra-embryonic endoderm of the VYS. Examination of gene and retrotranssposone expression and DNA methylation in extraembryonic, embryonic tissues and ES cell diferentiated as cystic EBs
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Project description:The rat is a widely used model for human physiology and psychology. However, due to their longer gestation periods and husbandry costs relative to mice, as well as the availability of superior molecular techniques to manipulate the mouse genome, relatively few genome-wide studies have been conducted in the rat. As such, a comprehensive analysis of genomic imprinting, which impacts complex traits such as growth and behaviour, has yet to be conducted in the rat. Towards this end, we systematically profiled embryonic and extra-embryonic tissue gene expression and DNA methylation with allele-specific resolution. We identified 14 embryonic and 26 extra-embryonic imprinted genes in the rat. Comparative analyses with mouse revealed that orthologous imprinted gene expression and associated canonical DNA methylation imprints are conserved in the embryo proper of the Muridae family. However, only 3 paternally expressed imprinted genes in the extra-embryonic embryo are conserved in Muridae, all of which are associated with non-canonical H3K27me3 imprints. The discovery of 8 novel candidate non-canonical imprinted genes unique to the rat is consistent with more rapid evolution of extra-embryonic imprinting. Cross-species analysis of novel rat imprinted genes with mouse and human revealed multiple mechanisms by which species-specific imprinted expression may be established, including H3K27me3 deposition in the oocyte, the birth of ZFP57 binding motifs and the insertion of endogenous retroviral promoters. Thus, characterization of the rat imprintome provides insights into the conservation of imprinted gene expression and the etiology of species-specific imprinting.
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Project description:To comprehensively delineate the ontogeny of an organ system, we generated 112,217 single- cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio- temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.
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