Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency

Fu, Meijun; Chen, Huan; Cai, Zepo; Yang, Yihang; Feng, Ziyu; Zeng, Meiqin; Chen, Lijun; Qin, Yue; Cai, Baomei; Zhu, Pinghui; Zhou, Chunhua; Yu, Shengyong; Guo, Jing; Liu, Jing; Cao, Shuiyan; Pei, Duanqing

doi:10.1186/s13619-021-00078-4

Cited by 16 publications

(10 citation statements)

References 42 publications

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“…Similarly, the DNA binding motif of the forkhead transcription factor FKH-10 was highly enriched in chromatin regions closing upon FACT depletion (Fig. 6a), which resonates with recent reports showing that Forkhead TFs are versatile regulators of cellular reprogramming to pluripotency (62). In human cells, Cactus identified not only FOS and CEBP but also STAT3 (Signal Transducer and Activator of Transcription 3) as TFs whose ChIP-Seq binding sites were highly enriched in chromatin regions opening upon FACT depletion (Fig.…”

Section: Cactus Could Confidently Predict a Role Of Fos In Regulating...supporting

confidence: 89%

Cactus: a user-friendly and reproducible ATAC-Seq and mRNA-Seq analysis pipeline for data preprocessing, differential analysis, and enrichment analysis

Salignon

Millán-Ariño

Garcia

et al. 2023

Preprint

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Summary: With the recent rapid advancements in sequencing technology, the analysis of omics data has become increasingly important for biomedical research. However, many laboratories lack the time or expertise to thoroughly analyze such data. Among omics assays, ATAC-Seq (Assay for transposase-accessible chromatin using sequencing) and mRNA-Seq (messenger RNA sequencing) are easy and cost-effective methods that are commonly used to define chromatin accessibility and gene expression levels, respectively. Here we introduce Cactus (Chromatin accessibility and transcriptomics unifying software), a pipeline that streamlines the individual or integrated analysis of ATAC-Seq and mRNA-Seq data. The pipeline is written in Nextflow for efficient scaling, caching, and parallelization, and all tools are packaged in Singularity/Docker containers or conda/Mamba virtual environments for simple installation and high reproducibility. Cactus conducts preprocessing on raw sequencing reads, followed by differential analysis between conditions. Results are split into Differential Analysis Subsets (DASs) based on significance threshold, direction of change, annotated genomic regions, and experiment type. Then, Cactus computes enrichments of entries from internal (i.e., DASs) and external (i.e., ontologies, pathways, DNA binding motifs, ChIP-Seq (Chromatin immunoprecipitation sequencing) binding sites, and chromatin states) databases in DASs and presents results in barplots and customizable heatmaps. The visualization of the results is simplified by the generation of merged PDFs, merged tables, and formatted Excel tables. In conclusion, Cactus can assist researchers in gaining comprehensive insights from chromatin accessibility and gene expression data in a quick, easy, and reproducible manner.

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Section: Cactus Could Confidently Predict a Role Of Fos In Regulating...supporting

confidence: 89%

Cactus: a user-friendly and reproducible ATAC-Seq and mRNA-Seq analysis pipeline for data preprocessing, differential analysis, and enrichment analysis

Salignon

Millán-Ariño

Garcia

et al. 2023

Preprint

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“…This would position FoxO TFs as a central cell fate switch that can both shield naïve identity and disrupt it under differentiation-permissive conditions. FoxO TFs are reported inhibitors of reprogramming to a naïve pluripotent ESC state (Fu et al 2021;Yu et al 2014). Our data indicate that the molecular reason for this effect could lie in the post-implantation-fate inducing function of FoxO TFs.…”

Section: Discussionmentioning

confidence: 65%

“…FoxO TFs are reported inhibitors of reprogramming to a naïve pluripotent ESC state (Fu et al 2021; Yu et al 2014). Our data indicate that the molecular reason for this effect could lie in the post-implantation-fate inducing function of FoxO TFs.…”

Section: Discussionmentioning

confidence: 99%

FoxO transcription factors actuate the formative pluripotency specific gene expression programme

Santini,

Kowald,

Sestini

et al. 2024

Preprint

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Naive pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naive pluripotency-specific transcription factors (TFs). Upon exiting naive pluripotency, ES cells transition through a formative post-implantation-like pluripotent state, where they acquire competence for lineage-choice. However, the mechanisms underlying disengagement from the naive GRN and initiation of the formative GRN are unclear. Here, we demonstrate that phosphorylated AKT acts as a gatekeeper that prevents nuclear localization of FoxO TFs in naive ESCs. PTEN-mediated reduction of AKT activity upon exit from naive pluripotency allows nuclear entry of FoxO TFs, enforcing a cell fate transition by binding and activating formative pluripotency-specific enhancers. Indeed, FoxO TFs are necessary and sufficient for transition from the naive to the formative pluripotent state. Our work uncovers a pivotal role for FoxO TFs and AKT signalling in mechanisms establishing formative post-implantation pluripotency, a critical early embryonic cell fate transition.

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“…Several mechanisms of action have been proposed for this effect, including increased reactive oxygen species, nitrotyrosine, matrix metalloproteinase, and decreased endothelial nitric oxide in response to antagonizing PPAR-gamma [ 82 ] and regulation of the Akt/FoxO3 pathway. More specifically, FoxO3 (forkhead box O3) is a member of the forkhead box transcription factors of the O class with a conserved helix-loop-helix DNA-binding domain; it is involved in a variety of vital cellular processes including oxidative stress, DNA repair, apoptosis, metabolism and cell cycle arrest [ 98 , 99 ]. Although the existing data are controversial, FoxO3 seem to play an important role in maintaining cardiovascular homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature

et al. 2022

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High levels of homocysteine (Hcy) have been linked with adverse cardiovascular outcomes, such as arrhythmias and stroke. In the context of paroxysmal atrial fibrillation (PAF), hyperhomocysteinemia has been demonstrated to be an independent predictor of future events. The aim of this report was to address the potential value of Hcy levels in predicting future paroxysms of atrial fibrillation (AF), as well as to identify the potential mechanisms of action. We searched PubMed and the Cochrane Database on 16 January 2022. Keywords used were homocysteine or hyperhomocysteinemia paired with a total of 67 different keywords or phrases that have been implicated with the pathogenesis of AF. We included primary reports of clinical and non-clinical data in the English language, as well as systematic reviews with or without meta-analyses. We placed no time constraints on our search strategy, which yielded 3748 results. Following title review, 3293 reports were excluded and 455 reports were used for title and abstract review, after which 109 reports were finally used for full-text review. Our review indicates that Hcy levels seem to hold a predictive value in PAF. Herein, potential mechanisms of action are presented and special considerations are made for clinically relevant diagnostic procedures that could complement plasma levels in the prediction of future PAF events. Finally, gaps of evidence are identified and considerations for future clinical trial design are presented.

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Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency

Cited by 16 publications

References 42 publications

Cactus: a user-friendly and reproducible ATAC-Seq and mRNA-Seq analysis pipeline for data preprocessing, differential analysis, and enrichment analysis

Cactus: a user-friendly and reproducible ATAC-Seq and mRNA-Seq analysis pipeline for data preprocessing, differential analysis, and enrichment analysis

FoxO transcription factors actuate the formative pluripotency specific gene expression programme

Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature

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