The CDP-Etn pathway accelerates mesenchymal-to-epithelial transition in somatic cell reprogramming
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ABSTRACT:
PROVIDER: PRJNA476964 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7405190_1.fastq.gz | Fastqsanger.gz | |||
| SRR7405190_2.fastq.gz | Fastqsanger.gz | |||
| SRR7405191_1.fastq.gz | Fastqsanger.gz | |||
| SRR7405191_2.fastq.gz | Fastqsanger.gz | |||
| SRR7405186_1.fastq.gz | Fastqsanger.gz |
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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
Project description:The transition from pluripotent to somatic states marks a critical event in mammalian development, but remains largely unresolved. Here we report the identification of SS18 as a regulator for pluripotent to somatic transition or PST by CRISPR-based whole genome screens. Mechanistically, SS18 forms microscopic condensates in nuclei through a C-terminal intrinsically disordered region (IDR) rich in tyrosine, which, once mutated, no longer form condensates nor rescue SS18-/- defect in PST. Yet, the IDR alone is not sufficient to rescue the defect even though it can form condensates indistinguishable from the wild type protein. We further show that its N-terminal 70aa is required for PST by interacting with BAF complex, and remains functional even swapped onto unrelated IDRs or even an artificial 24 tyrosine polypeptide. Finally, we show that SS18 mediates BAF assembly through phase separation to regulate PST. These studies suggest that SS18 plays a role in the pluripotent to somatic interface and undergoes liquid-liquid phase separation through a unique tyrosine-based mechanism.
2021-05-23 | PXD026208 |
Project description:Obesity Accelerates Endothelial-to-Mesenchymal Transition in Adipose Tissue of Mice and Humans
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Project description:Mammalian oocytes possess fascinating unknown factors, which can reprogram terminally differentiated germ cells (sperm) or somatic cells into totipotent embryos. Here, we demonstrate that oocyte specific homeobox 1 (Obox1), an oocyte-specific factor, can markedly enhance the generation of induced pluripotent stem cells (iPSCs) from mouse fibroblasts in a proliferation-independent manner and can replace Sox2 to achieve pluripotency. Overexpression of Obox1 can greatly promote mesenchymal-to-epithelial transition (MET) at early stage of OSKM-induced somatic cell reprogramming and meanwhile, the cell hyper-proliferation can be significantly slowed down. Subsequently, the proportion of Thy1 negative cells and Oct4-GFP positive cells increased dramatically. Further analysis of gene expression and targets of Obox1 during reprogramming indicates that the expression of Obox1 can promote epithelial genes expression and repress cell cycle-related genes expression. Taken together, we conclude that the oocyte-specific factor Obox1 serves as a strong activator for somatic cell reprogramming through promoting the MET and mitigating cells hyper-proliferation.
2017-09-21 | GSE97859 | GEO
Project description:Epithelial-mesenchymal transition (EMT) and its critical roles during cancer progression have long been recognized and extensively reviewed. Recent studies on the generation of induced pluripotent stem cells (iPSCs) have established the connections among EMT, energy metabolism, DNA methylation, and histone modification. Since energy metabolism, DNA methylation, and histone modification are important for cancer development and there are common characteristics between cancer cells and stem cells, it is reasonable to identify mechanisms that have been established during both reprogramming and cancer progression. In the current review, we start from a brief review on EMT and related processes during cancer progression, and then switch to the EMT during somatic cell reprogramming. We summarize the connection between EMT and metabolic switch during reprogramming, and further review the involvements of DNA methylation and cell proliferation. The connections between EMT and mesenchymal-epithelial transition (MET) and cellular aspects including DNA methylation, histone modification and energy metabolism may provide potential new targets for cancer diagnosis and treatment.
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Project description:This SuperSeries is composed of the following subset Series: GSE27968: DNA methylation data from AML12 cells during EMT GSE28291: Genome-scale epigenetic reprogramming during epithelial to mesenchymal transition Refer to individual Series
2011-07-03 | E-GEOD-28581 | biostudies-arrayexpress
Project description:The exit from pluripotency or pluripotent-somatic transition (PST) landmarks an event of mammalian development, and is also a representative cell-fate transition model, but remains largely unresolved. Recently, we reported construction of robust JUN-induced PST completed in one cell cycle and whose dominant regulator SS18/BAFs (Brg1/Brahma-associated factors). However, the transition process in the chromatin architecture and the roles played by BAF are still unknown. Here we report the dynamic changes of chromatin accessibility during JUN-induced PST. Meanwhile, SS18/BAFs mediates PST process by relocating from pluripotent loci to AP-1 associated ones and once compromised, JUN fails to open chromatin and PST will be delayed. Furthermore, we show that the relocation of SS18/BAF partially relays on histone modification H3K27ac, instead of JUN-centric protein-protein interaction. These results reveal the orchestration of master transcription factor, epigenetic machine, and histone modification in the cell fate transition.
2021-10-22 | PXD029277 |
Project description:BackgroundIdentifying novel regulatory factors and uncovered mechanisms of somatic cell reprogramming will be helpful for basic research and clinical application of induced pluripotent stem cells (iPSCs). Sin3a, a multifunctional transcription regulator, has been proven to be involved in the maintenance of pluripotency in embryonic stem cells (ESCs), but the role of Sin3a in somatic cell reprogramming remains unclear.MethodsRNA interference of Sin3a during somatic cell reprogramming was realized by short hairpin RNAs. Reprogramming efficiency was evaluated by the number of alkaline phosphatase (AP)-positive colonies and Oct4-GFP-positive colonies. RNA sequencing was performed to identify the influenced biological processes after Sin3a knockdown and further confirmed by quantitative RT-PCR (qRT-PCR), western blotting and flow cytometry. The interaction between Sin3a and Tet1 was detected by coimmunoprecipitation. The enrichment of Sin3a and Tet1 at the epithelial gene promoters was measured by chromatin immunoprecipitation. Furthermore, DNA methylation patterns at the gene loci were investigated by hydroxymethylated DNA immunoprecipitation. Finally, Sin3a mutants that disrupt the interaction of Sin3a and Tet1 were also introduced to assess the importance of the Sin3a-Tet1 interaction during the mesenchymal-to-epithelial transition (MET) process.ResultsWe found that Sin3a was gradually increased during OSKM-induced reprogramming and that knockdown of Sin3a significantly impaired MET at the early stage of reprogramming and iPSC generation. Mechanistic studies showed that Sin3a recruited Tet1 to facilitate the hydroxymethylation of epithelial gene promoters. Moreover, disrupting the interaction of Sin3a and Tet1 significantly blocked MET and iPSC generation.ConclusionsOur studies revealed that Sin3a was a novel mediator of MET during early reprogramming, where Sin3a functioned as an epigenetic coactivator, cooperating with Tet1 to activate the epithelial program and promote the initiation of somatic cell reprogramming. These findings highlight the importance of Sin3a in the MET process and deepen our understanding of the epigenetic regulatory network of early reprogramming.
| S-EPMC8785580 | biostudies-literature
Project description:During somatic reprogramming, Yamanaka's pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here, we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2 inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial to the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in the chromatin landscape ultimately lead to a deregulation of key genes that are important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events that are necessary for changes in cell fate identity during the reprogramming process.
| S-EPMC6092268 | biostudies-literature
Project description:The generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming holds great potential for modeling human diseases. However, the reprogramming process remains very inefficient and a better understanding of its basic biology is required. The mesenchymal-to-epithelial transition (MET) has been recognized as a crucial step for the successful reprogramming of fibroblasts into iPSCs. It has been reported that the p53 tumor suppressor gene acts as a barrier of this process, while its homolog p63 acts as an enabling factor. In this regard, the information concerning the role of the third homolog, p73, during cell reprogramming is limited. Here, we derive total Trp73 knockout mouse embryonic fibroblasts, with or without Trp53, and examine their reprogramming capacity. We show that p73 is required for effective reprogramming by the Yamanaka factors, even in the absence of p53. Lack of p73 affects the early stages of reprogramming, impairing the MET and resulting in altered maturation and stabilization phases. Accordingly, the obtained p73-deficient iPSCs have a defective epithelial phenotype and alterations in the expression of pluripotency markers. We demonstrate that p73 deficiency impairs the MET, at least in part, by hindering BMP pathway activation. We report that p73 is a positive modulator of the BMP circuit, enhancing its activation by DNp73 repression of the Smad6 promoter. Collectively, these findings provide mechanistic insight into the MET process, proposing p73 as an enhancer of MET during cellular reprogramming.
| S-EPMC5636977 | biostudies-literature