Mus musculus
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PROVIDER: PRJNA187048 | ENA |
REPOSITORIES: ENA
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Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2018-08-02 | MSV000082680 | GNPS
Project description:Following implantation, mouse epiblast cells transit from a naïve to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from naïve pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naïve pluripotency expression program through the decommissioning of active enhancers associated with key naïve pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from naïve pluripotency and subsequent PGC specification. mRNA profiles were generated by RNA-seq in duplicates for each of the following mESC lines: Foxd3fl/fl;Cre-ER mESC maintained in "Serum+LIF" (SL) treated with TM for three days (SL Foxd3-/-); untreated Foxd3fl/fl;Cre-ER SL mESC (SL Foxd3fl/fl); tetON Foxd3 SL mESC treated with Dox for three days; WT SL mESC treated with Dox for three days; Foxd3fl/fl;Cre-ER mESC maintained in "2i+LIF" (2i) treated with TM for three days (2i Foxd3-/-); untreated Foxd3fl/fl;Cre-ER 2i mESC (2i Foxd3fl/fl).
2015-09-14 | E-GEOD-70546 | biostudies-arrayexpress
Project description:Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (mEpiSCs). The mEpiSC medium which contains Activin A and bFGF induces differentiation of mouse embryonic stem cells (mESCs) to mEpiSC. Here we show that Activin A also has an ability to efficiently propagate mESCs without differentiation to mEpiSCs when combined with a MEK inhibitor PD0325901. mESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors. Genome-wide analysis revealed that the gene expression profile of mESCs cultured in Activin+PD resembles that of mESCs cultured in 2i. mESCs cultured in Activin+PD also showed features which are related to naive pluripotency of mESCs, including the preferential usage of the Oct4 distal enhancer and the self-renewal response to Wnt pathway activation. Our finding reveals a role of Activin/Nodal/TGF-β signaling in stabilizing self-renewal gene regulatory networks in mESCs. To compare the gene expression patterns of mESCs cultured in Activin+PD, 2i and LIF+BMP4 and mEpiSCs, we performed genome-wide gene expression analysis by using Affymetrix GeneChip oligonucleotide microarrays
2019-07-11 | GSE84679 | GEO
Project description:The inner cell mass of the mouse pre-implantation blastocyst is comprised of epiblast progenitor and primitive endoderm cells of which cognate embryonic (mESCs) or extra-embryonic (XEN) stem cell lines can be derived. Importantly, each stem cell type retains the defining properties and lineage restriction of their in vivo tissue of origin. Recently, we demonstrated that XEN-like cells arise within mESC cultures. This raises the possibility that mESCs can generate self-renewing XEN cells without the requirement for gene manipulation. We have developed a novel approach to convert mESCs to XEN cells (cXEN) using growth factors. We confirm that the down-regulation of the pluripotency transcription factor Nanog and the expression of primitive endoderm-associated genes Gata6, Gata4, Sox17 and Pdgfra are necessary for cXEN cell derivation. This approach highlights an important function for Fgf4 in cXEN cell derivation. Paracrine FGF-signalling compensates for the loss of endogenous Fgf4, which is necessary to exit mESC self-renewal, but not for XEN cell maintenance. Our cXEN protocol also reveals that distinct pluripotent stem cells respond uniquely to differentiation promoting signals. cXEN cells can be derived from mESCs cultured with Erk- and Gsk3-inhibitors (2i) and LIF, similarly to conventional mESCs. However, we find that epiblast stem cells (EpiSCs) derived from the post-implantation embryo are refractory to cXEN cell establishment, consistent with the hypothesis that EpiSCs represent a pluripotent state distinct from mESCs. In all, these findings suggest that the potential of mESCs includes the capacity to give rise to both extra-embryonic and embryonic lineages. A total of eight samples were analyzed. Three mouse embryonic stem cell (mESC) lines were used as a negative control, 2 embryo-derived extraembryonic endoderm (XEN) cell lines were used as a positive control, 3 converted XEN (cXEN) cells were used as the experiemental cell lines.
2012-06-04 | E-GEOD-38477 | biostudies-arrayexpress
Project description:In this study we have analyzed the global gene expression of naïve mouse embryonic stem cells in different culture conditions including R2i (PD0325901+SB431542), 2i (PD0325901+CHIR99021), and also PD0325901+LIF and SB431542+LIF to show the similarities and differences between the conditions in maintaining pluripotency. Since the first generation of mouse embryonic stem (ES) cells, extrinsic regulation of pluripotency has been at the focus of attention. Here we show that suppression of transforming growth factor β (TGFβ) signaling could have impressive effects on self-renewal and pluripotency of mouse ES cells. We introduce a chemically defined medium with inhibitors of TGFβ and mitogen-activated protein kinase (MAPK) kinase, designated here as R2i (Royan 2 inhibitors), for highly efficient establishment of ES cell lines from various mouse strains. R2i also supports homogenous expression of Nanog and Dppa3 proteins in ES cells and shows minimal differentiation leakage. Our results uncover an appropriate condition for ES cell generation from single blastomeres of various cleavage-stage embryos. Further, the high accuracy of genome integrity after long-term cultivation in R2i illustrates an optimal condition for ES cell culture. Global transcriptomic analysis of R2i cells demonstrates that bone morphogenetic protein 4 (BMP4) signaling becomes overrepresented pursuant to TGFβ repression, which may confer further robustness to pluripotency through shielding cells from differentiation stimuli. These findings point to a new facet of ground state pluripotency by blocking differentiation pathways, without influencing the pluripotency regulatory circuitry of mouse ES cells. Whole gene expression study of 4 different mouse embryonic stem cell lines maintained under 4 different chemically defined conditions: R2i, 2i, PD and SB
2013-10-21 | E-GEOD-43682 | biostudies-arrayexpress
Project description:We describe here the proteome of mouse embryonic stem cells growth in complete media (KSR, LIF/2i) or media without 2i for 24h and 48h.
2025-06-23 | PXD033005 | Pride
Project description:Pluripotent mouse embryonic stem cells (ESCs) were originally derived and stably maintained on feeder cells such as inactivated mouse embryo fibroblasts, and can generate complete ESC-pups by tetraploid embryo complementation (TEC), the most stringent functional test of naive pluripotency. Remarkably, 2i (inhibitors of Mek and Gsk3β signaling) medium with LIF in the absence of serum and feeders was developed to achieve ground state of mouse ESCs, and also has been successfully used for derivation of germline competent ESCs in other species such as rat. Notably, 2i-culture gives rise to transcriptional profiles and epigenetic landscapes quite distinct from serum-based ESCs. To better understand transcriptional landscape and signal transductions, we performed RNA-seq analysis of ESCs cultured in four different conditions: serum without feeder, serum with feeder, serum with feeder and 2i, and N2B27+2i.
2018-01-20 | GSE109418 | GEO
Project description:lncRNA profiles of ground state mouse embryonic stem cells cultured in 2i condition.
2017-12-30 | GSE87632 | GEO
Project description:The ground state of pluripotency is defined as a basal proliferative state free of epigenetic restriction, represented by mouse embryonic stem cells (ESCs) cultured with two kinase inhibitors (so-called “2i”). Through comparison with serum-grown ESCs, we identify epigenetic features characterizing 2i ESCs by proteome profiling of chromatin including post-translational histone modifications. The most prominent difference is H3K27me3 and its enzymatic writer complex PRC2 that are highly abundant on eu- and heterochromatin in 2i ESCs, with H3K27me3 redistributing outside canonical PRC2 targets in a CpG-dependent fashion. Using PRC2-deficient 2i ESCs, we identify epigenetic crosstalk with H3K27me3, including significant increases in H4 acetylation and DNA methylation. This suggests that the unique H3K27me3 configuration protects 2i ESCs from preparation to lineage priming. Interestingly, removal of DNA methylation in PRC2-deficient 2i ESCs lacking H3K27me3 using 5-azacytidine hardly affected ESC viability and transcriptome, showing that ESCs are independent of both major repressive epigenetic marks.
2018-11-21 | PXD007154 | Pride
Project description:We apply deep small-RNA sequencing technology for high-throughput profiling of microRNAs in ground state embryonic stem cells (ESCs). We provide global expression signatures of microRNAs in ESCs cultured under serum, 2i, and R2i conditions. We report that microRNAs are significantly differentially expressed when ESCs are cultured under different conditions, and that ground state pluripotency features a uniqure microRNA signature which is mainly encoded by microRNA-coding sequences within the developmentally important DLK1-Dio3 locus. Finally, we indicate that microRNA upregulated in ground state pluripotent cells (i.e. 2i/R2i) contribute to the maintenace of ground state pluripotency through stimulating self-renewal and inhibiting multi-lineague differentiation.
2017-09-21 | GSE87174 | GEO