Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes, ID1, BCL2L1 and HM13, expressed in human ES cells, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.

BackgroundSelective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary for maintaining the DNA methylation memory at multiple imprinting control regions in early mouse embryos and embryonic stem (ES) cells. Maternal-zygotic deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth. Additionally, several cases of human transient neonatal diabetes are associated with somatic mutations in the ZFP57 coding sequence.ResultsHere, we comprehensively map sequence-specific ZFP57 binding sites in an allele-specific manner using hybrid ES cell lines from reciprocal crosses between C57BL/6J and Cast/EiJ mice, assigning allele specificity to approximately two-thirds of all binding sites. While half of these are biallelic and include endogenous retrovirus (ERV) targets, the rest show monoallelic binding based either on parental origin or on genetic background of the allele. Parental-origin allele-specific binding is methylation-dependent and maps only to imprinting control differentially methylated regions (DMRs) established in the germline. We identify a novel imprinted gene, Fkbp6, which has a critical function in mouse male germ cell development. Genetic background-specific sequence differences also influence ZFP57 binding, as genetic variation that disrupts the consensus binding motif and its methylation is often associated with monoallelic expression of neighboring genes.ConclusionsThe work described here uncovers further roles for ZFP57-mediated regulation of genomic imprinting and identifies a novel mechanism for genetically determined monoallelic gene expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0672-7) contains supplementary material, which is available to authorized users.

Proportion and pathways of the eddy-induced heat transport are critical in maintaining world’s ocean and climate states. However, an observation-based three-dimensional picture of how oceanic eddies contribute to the global heat transport is yet not quantitatively specified, particularly due to insufficiency of data. Here, using refined methods, we have achieved this goal by analyzing millions of high-quality Argo hydrographic profiles and high-resolution satellite altimetric data. We first presented the spatial differences of individual eddies by reconstructing 254 representative eddies all over the ocean, and then calculated heat fluxes associated with eddies in 5° × 5° boxes. It is revealed that all parameters of eddies vary significantly with both latitudes and longitudes, which is crucial in yielding spatially varying heat fluxes and transports. The eddies not only transport heat towards high latitudes (down-gradient), but also towards low latitudes (up-gradient), particularly at subsurface layers of mid-latitude northern Pacific Ocean and low-latitude Atlantic Ocean. The eddy heat transport is mainly confined in the upper 1000 m of the western part and mid-latitudes of the world’s ocean basins, coinciding with maximum meridional temperature gradients. It peaks at 0.8 PW and 0.3 PW (1 PW = 1015 W) at 45°S and 35°N, respectively, stronger than previous estimates based on model results, and accounts for about one half and one third of the estimated total oceanic heat transport at the same latitudes, respectively. In any location except for the areas associated with the Antarctic Circumpolar Current, the eddy stirring component is distinctly (1–10 times) larger than the eddy trapping component.