Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA402072 | ENA |
REPOSITORIES: ENA
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Project description:The role of Striatin Interacting Protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Strip2 silenced (KD) ESCs were differentiated for 4, 8, 12, and 16 days. We show that Strip2 is distributed in the perinucleus or nuclei of wild type (WT) undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. CellNet analysis of microarray gene expression data for KD and scrambled control (SCR) embryoid bodies (EBs), as well as immunostainings of key pluripotent factors, demonstrated that KD ESCs remain undifferentiated. This occurs even in 16-day old EBs, which possessed a high tumorigenic potential. Correlated with very high expression levels of epigenetic regulator genes, Hat1 and Dnmt3, enzymatic activities of the histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3 beta (DNMT3b) were higher in differentiated 16-day old KD EBs than in SCR or WT EBs. The expression levels of let-7, 290 and 302 microRNA families were opposed in KD ESCs, while KD EBs had levels comparable to WT and SCR ESCs during differentiation. This demonstrates that Strip2 is critical to the onset of differentiation, regulating expression of epigenetic regulators, HAT1 and DNMT3b, as well as microRNAs involved in pluripotency.
2017-03-26 | GSE96807 | GEO
Project description:The role of Striatin Interacting Protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Strip2 silenced (KD) ESCs were differentiated for 4, 8, 12, and 16 days. We show that Strip2 is distributed in the perinucleus or nuclei of wild type (WT) undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. CellNet analysis of microarray gene expression data for KD and scrambled control (SCR) embryoid bodies (EBs), as well as immunostainings of key pluripotent factors, demonstrated that KD ESCs remain undifferentiated. This occurs even in 16-day old EBs, which possessed a high tumorigenic potential. Correlated with very high expression levels of epigenetic regulator genes, Hat1 and Dnmt3, enzymatic activities of the histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3 beta (DNMT3b) were higher in differentiated 16-day old KD EBs than in SCR or WT EBs. The expression levels of let-7, 290 and 302 microRNA families were opposed in KD ESCs, while KD EBs had levels comparable to WT and SCR ESCs during differentiation. This demonstrates that Strip2 is critical to the onset of differentiation, regulating expression of epigenetic regulators, HAT1 and DNMT3b, as well as microRNAs involved in pluripotency. For a more comprehensive understanding of the potential effects of miRNA for heart development, we carried out the first study of time-resolved parallel profiling of mRNA and miRNA levels in the developing and adult (10 weeks old) as well as old (14 months old) murine heart and identify the dynamical activation or repression of numerous biological processes and signalling pathways
2017-03-26 | GSE96808 | GEO
Project description:The Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We recently have identified one of the MAGE gene members, Mageb16 to be highly expressed in undifferentiated murine embryonic stem cells (mESCs). The role of Mageb16 for the differentiation of the pluripotent stem cells is completely unknown. Here we demonstrate that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated mESCs. A transcriptome study was performed with differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD ESCs) and scrambled control (SCR) ESCs until a period of 22 days. Mageb16 KD ESCs mainly differentiated towards mesodermal derivatives such as cardiovascular lineages. Mesoderm-oriented differentiation initiated biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were significantly enriched in the differentiated Mageb16 KD ESCs. Cardiomyogenesis in differentiated KD mESCs was stronger when compared to differentiated SCR and wild mESCs. The expression of non-coding RNA (ncRNA) Lin28a and other epigenetic regulatory genes, nucleocytoplasmic trafficking and genes participating in spermatogenesis have also declined faster in the differentiating Mageb16 KD ESCs. We conclude that Mageb16 plays a crucial role for differentiation of ESCs, specifically to the mesodermal lineages. Regulative epigenetic networks and nucleocytoplasmic modifications induced by Mageb16 may play a role for the critical role of Mageb16 for the ESCs differentiation.
2017-09-13 | GSE103615 | GEO
Project description:Genome-wide profiling of miRNAs during differentiation of wild (WT) murine embryonic stem cells (ESCs), scrambled control (SCR) ESCs, and Strip2 silenced (KD) ESCs
| PRJNA379784 | ENA
Project description:Genome-wide profiling of genes during differentiation of wild (WT) murine embryonic stem cells (ESCs), scrambled control (SCR) ESCs, and Strip2 silenced (KD) ESCs
| PRJNA379783 | ENA
Project description:Genome-wide profiling of genes and miRNAs during differentiation of wild (WT) murine embryonic stem cells (ESCs), scrambled control (SCR) ESCs, and Strip2 silenced (KD) ESCs
| PRJNA379779 | ENA
Project description:Gene expression of murine repeatedly activated Th1 cells 36h, 48h and 72h after miR-31 inhibition using a specific antagomir (Antagomir-31) compared to a scrambled controll (Antagomir-SCR).
2018-12-19 | GSE122223 | GEO
Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) and are dynamically expressed in various embryonic and adult cell types. While loss of individual Tet enzymes or combined deficiency of Tet1/2 allows for embryogenesis, the effect of complete loss of Tet activity and 5hmC marks in development is not established. We have generated Tet1/2/3 triple knockout (TKO) mouse embryonic stem cells (ESCs) and examined their developmental potential. Combined deficiency of all three Tets depleted 5hmC and impaired ESC differentiation as seen in poorly differentiated TKO embryoid bodies (EBs) and teratomas. Consistent with impaired differentiation, TKO-ESCs contributed poorly to chimeric embryos and could not support embryonic development. Global gene expression and methylome analyses of TKO-EBs revealed promoter hypermethylation and deregulation of genes implicated in embryonic development and differentiation. These findings suggest a requirement for Tet- and 5hmC-mediated DNA demethylation in proper regulation of gene expression during differentiation of ESCs and development. To quantify global gene expression in differentiating embryoid bodies (EBs) derived from wild type (WT) and Tet triple knockout (TKO), TKO and WT mouse embryonic stem cells (ESCs) were differentiated in vitro to EBs and cultured for 10 days. RNA was extracted using Qiagen RNeasy kit and subjected to microarray analysis. Global gene expression profile of two technical replicas of WT embryoid bodies (2 samples in total) was compared to two technical replicas of two independent TKO embryoid bodies (4 TKO samples in total).
2014-04-14 | E-GEOD-55574 | biostudies-arrayexpress
Project description:Polycomb group (PcG) proteins comprise a large group of evolutionary conserved factors with essential roles for embryonic development and adult stem cell function. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene expression. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (PCGF) paralogs. So far, six PCGF paralogs (PCGF1-6) have been identified but paralog-specific functions are not well understood. In our studies, we observed that Pcgf6 showed the highest expression level in undifferentiated murine embryonic stem cells (ESCs), blastocysts and testes. When ESCs differentiated, Pcgf6 expression strongly declined. To further investigate Pcgf6 biology, we established dox-inducible shRNA knockdown (KD) ESCs. Following Pcgf6 KD in ESCs the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were de-repressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities. Finally, PCGF6 replaced SOX2 but not KLF4 or c-MYC in the generation of germline-competent iPS cells. Forced expression of Pcgf6 in OSKM-driven reprogramming increases iPS efficiency while Pcgf6 KD reduces the formation of ESC-like colonies. Together, these analyses show that Pcgf6 is non-redundantly involved in maintaining the pluripotent nature of ESCs and functions in iPS reprogramming. 6 samples were hybridized GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix)
2014-09-26 | E-GEOD-56126 | biostudies-arrayexpress
Project description:The decline in stem cell function leads to impairments in tissue homeostasis but genetic factors that control differentiation and de-differentiation of stem cells in the context of tissue homeostasis remain to be delineated. Here we show that Tnfaip2 (a target gene of TNFa/NFkB signaling) has an essential role for the differentiation of pluripotent, embryonic stem cells (ESCs). Knockdown of the planarian pseudo-orthologue, Smed-exoc3, impairs pluripotent stem cell differentiation, tissue homeostasis and regeneration in vivo. The study shows that Tnfaip2 deletion impairs changes in lipid metabolism that drive differentiation induction of ESCs. The application of palmitic acid (PA, the most abundant saturated fatty acid in mammalian cells) and palmitoylcarnitine (a mitochondrial carrier of PA) fully restores the differentiation of ESCs as well as the differentiation of pluripotent stem cells and organ maintenance in Smed-exoc3-depleted planarians. Together, these results identify a novel pathway downstream of TNFa/NFkB signaling, which is essential for exit from pluripotency by mediating changes in lipid metabolism.
2020-11-18 | PXD014628 | Pride