Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA400566 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Resolving the function of FoxO6 during Somatic Cell Reprogramming by RNA-seq
| PRJNA675389 | ENA
Project description:Cell fate transitions involve rapid changes of gene expression patterns and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we used transcription-factor induced reprogramming of somatic cells into pluripotent cells to screen for novel regulators of cell fate change. We identified the RNA processing factor Nudt21, a component of the pre-mRNA cleavage and polyadenylation complex, as a potent barrier to reprogramming. Importantly, suppression of Nudt21 not only enhanced the generation of induced pluripotent stem cells but also facilitated the conversion of fibroblasts into trophoblast stem cells and delayed the differentiation of myeloid precursor cells into macrophages, suggesting a broader role for Nudt21 in restricting cell fate change. Polyadenylation site sequencing (PAS-seq) revealed that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency. While only a fraction of these transcripts changed expression at the protein level, this fraction was strongly enriched for chromatin regulators, including components of the PAF, polycomb, and trithorax complexes. Co-suppression analysis further suggests that these chromatin factors are largely responsible for Nudt21’s effect on reprogramming, providing a mechanistic basis for our observations. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of mammalian cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.
2018-01-08 | PXD008078 | Pride
Project description:The somatic cell fate can be converted to tumor or pluripotent ones by ectopic expression of transcription factors in vitro and in vivo. Many oncogenic transcription factors are known to mediate both fates as they share similar proliferative and metabolic properties. Paradoxically, we found c-Jun as the first oncogene that appears to specify a somatic fate, oppose the pluripotent one and impede reprogramming. We performed a series of high through out sequencing to understand the way cJun works. To understand how c-Jun drives mESCs differentiating, we obtained c-Jun TetOn mESCs, and performed RNAseq 36h later with dox inducing or not . To understand why c-Jun blocks reprogramming while c-JunDN and Jdp2 can replace Oct4, we overexpressed these factors with KSM during reprogramming and performed RNAseq 3 Days after virus transfection. Moreover, to extend understand how these factors regulate gene expression, we also overexpressed these factors in MEF and performed RNAseq. Further more, to understand how cJun regulates cell fates and gene expression, we overexpressed c-Jun in mouse ESC and performed ChIP-seq. Also, we performed c-JunDN ChIP-seq during somatic cells reprogramming on day 3, to explore the binding sites of c-JunDN.
2015-06-10 | E-GEOD-50776 | biostudies-arrayexpress
Project description:Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate, using reprogramming efficiency towards iPSCs as an assay. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.
2019-09-19 | GSE127932 | GEO
Project description:Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate, using reprogramming efficiency towards iPSCs as an assay. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.
2019-09-19 | GSE127930 | GEO
Project description:Single-cell landscape of transcriptional heterogeneity and cell fate decisions during mouse early gastrulation
| PRJNA392258 | ENA
Project description:Tet1 is a hydroxylase known for its role in the conversion of 5-methylcytosines (5mC) to 5-hydroxymethylcytosines (5hmC) involved in the possible active demethylation process and gene expression regulation1-5.M-BM- As somatic cell reprogramming involves the re-activation of pluripotency genes and the silencing of somatic ones6, it remains unclear whether Tet1 plays a positive or negative role in the reprogramming process. Here we show that Tet1 deficiency enhances reprogramming and its overexpression impairs reprogramming. Mechanistically, we demonstrated that Tet1 represses the early obligatory process of mesenchymal to epithelial transition (MET) during reprogramming7,8. Thus, our findings not only define a negative role for Tet1 in somatic cell reprogramming, but also suggest that the Tet enzymes regulate cell fate through distinctive mechanisms. Examination of genome DNA hmC modifications in 2 conditions: individually overexpressed Tet1CD or Tet2CD during MEF reprogramming; Examination of mRNA levels in five different conditions: individually overexpressed DR or Tet1CD or Tet1CDmut or Tet2CD or Tet2CDmut, during MEF reprogrammig.
2013-03-08 | E-GEOD-44935 | biostudies-arrayexpress
Project description:O-GlcNAc Homeostasis Controls Cell Fate Decisions During Hematopoiesis
| PRJNA503593 | ENA
Project description:Metabolic reprogramming has emerged as key regulators of cell fate decisions. Whereas the glucose and amino acid metabolism have been extensively documented, the roles of lipid metabolism in pluripotency remain largely unexplored. Here, we report that the CDP-Ethanolamine (CDP-Etn) pathway for phosphatidylethanolamine synthesis is required for somatic cell reprogramming at the early stage. Mechanistically, the CDP-Etn pathway inhibits NF-κB signaling and mesenchymal genes in a Pebp1 dependent manner, resulting in accelerated mesenchymal-to-epithelial transition and enhanced reprogramming. In addition, we show that phospholipids are critical for the growth of mESC though without effects on pluripotency. Our study reveals an unforeseen connection between phospholipids, cell migration and pluripotency and highlights the importance of phospholipids in cell fate transitions.
2019-08-25 | GSE116080 | GEO