Critical Role of Runx Transcription Factors in Maintaining Epididymal Epithelial Differentiation [RNA-seq II]
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ABSTRACT:
PROVIDER: PRJNA989043 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25068714_1.fastq.gz | Fastqsanger.gz | |||
| SRR25068714_2.fastq.gz | Fastqsanger.gz | |||
| SRR25068715_1.fastq.gz | Fastqsanger.gz | |||
| SRR25068715_2.fastq.gz | Fastqsanger.gz | |||
| SRR25068716_1.fastq.gz | Fastqsanger.gz |
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Project description:Critical Role of Runx Transcription Factors in Maintaining Epididymal Epithelial Differentiation
| PRJNA989033 | ENA
Project description:To study the role of RUNX transcription factors in the epididymal epithelial cells we deleted Runt domains of Runx1 and Runx2 from mouse epididymal cell line mE-Cap18 using CRISPR-Cas9 technique.
2024-05-02 | GSE236104 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-02 | GSE236105 | GEO
Project description:Runx transcription factors are essential for generating functional T cells starting from the earliest stages in thymic T-development. To evaluate how Runx factors instruct T cell development, we perturbed Runx activities using 1) CRISPR-Cas9, simultaneously deleting two predominant, redundant Runx factors, Runx1 and Runx3, and 2) Runx1-overepxression at a stage before pro-T cells commit to a T cell fate. Then single-cell transcriptome analysis was performed. Runx1/Runx3 knockout (KO) vs. Runx1 overexpression (OE) resulted in contrasting deviations from the normal developmental trajectory. The separation of both perturbation conditions from the controls implied that Runx factors regulate gene networks in individual cells to control separate pathways instead of changing distributions of cells among different stages along the control pathway. Notably, a common core set of genes responded to both KO and OE, in opposite directions. Runx activation target genes were selectively enriched for T-identity program and innate lymphoid cell program genes, whereas inhibition targets were significantly associated with stem/progenitor program and myeloid lineage pathways. Pseudotime inference analysis suggested that Runx perturbations also substantially regulate developmental speed, as Runx KO significantly slowed down developmental progression, whereas Runx1 OE resulted in pronounced acceleration. This interpretation was largely supported by Runx activities regulating key transcription factors involved in establishing distinct gene network modules during T cell development. Indeed, further analysis showed that Runx target genes get combinatorial inputs from these Runx-regulated transcription factors as well as from Runx factors themselves. Together, our data suggest that Runx transcription factors drive early T developmental progression by launching gene expression modules associated with T-identity and innate lymphoid cells through mediating other transcription factor cooperativities.
2023-07-09 | GSE218149 | GEO
Project description:An antagonistic interplay between YAP and RUNX where RUNX proteins abrogate YAP-mediated transcription of EMT and Stemness associated genes in mammary epithelial cells in an interaction dependent manner.
2018-02-26 | GSE60876 | GEO
Project description:Runx1 and Runx3 function redundantly in early T-development, and together drive T-lineage developmental progression by regulating distinct sets of genes in different stages. Context-specific Runx target genes are particularly enriched near Runx binding sites that dynamically shift from pre-T-commitment stages (Phase 1) to post-T-commitment stages (Phase 2). As total Runx activities (Runx1+Runx3) are maintained stably throughout early T-development stages, yet Runx factors physically interact with multiple collaborators, we hypothesized that different Runx-collaborating transcription factors compete to recruit a limited pool of Runx transcription factors. To test whether increasing Runx availability can alter Runx DNA-binding site choices, Runx1 overexpression vectors were introduced to two different systems. First, we increased Runx1 expression in a DN3-like cell line (representing a post-commitment, Phase 2 stage) in the presence or absence of exogenous Phase 1 co-factor, PU.1. Second, we increased Runx1 expression in Phase 1 primary cells which naturally express PU.1 and other Phase 1 collaborators. Then, Runx1 binding behaviors were measured using ChIP-seq or CUT&RUN (C&R). A modest increase of Runx1 levels (about 2-3 fold increase) substantially increased the number of Runx binding sites seen and the intensity of occupancy in both systems. When Runx expression was at physiological levels, PU.1 dominated Runx1 site choice before T commitment by recruiting Runx1 to PU.1 sites. The Phase 2 cell line system showed that it did this while depleting Runx1 from alternative high quality Runx motif sites. However, when Runx1 was overexpressed, Runx1 was still recruited to PU.1 sites, but this recruitment did not evacuate Runx1 occupancy from default preferred sites. Notably, Runx1 overexpression in primary Phase 1 cells caused precocious occupancy of post-commitment, Phase 2-specific sites. We found that these are often co-occupied with TCF1, E2A, and HEB, but have minimal co-binding with PU.1. In addition, Runx1 overexpression resulted in new binding sites that were not normally observed in pro-T cells, which are mostly sequestered by closed chromatin normally although they harbor more numerous Runx motifs. Thus, these data suggest that Runx DNA binding site choices are sensitive to Runx concentration and co-factors during early T-development.
2023-07-09 | GSE218147 | GEO
Project description:The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour supressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins reflecting the marked effects of Runx on cell adhesion. Keywords: Comparative study of gene targets regulated by overexpression of the different Runx family members
2008-06-12 | GSE11732 | GEO
Project description:The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour supressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins reflecting the marked effects of Runx on cell adhesion. Experiment Overall Design: 6 samples (expression of different Runx family members); 5 in duplicate, 1 single. 2 control samples (empty vector) in duplicate. Cultures of Runx expressing cells were grown to confluence, treated with ethanol +/- 4OHT tamoxifen for 24 hours and harvested for RNA extraction and hybridization on Affymetrix microarrays
2008-10-21 | E-GEOD-11732 | biostudies-arrayexpress
Project description:Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. Therefore, there should be mechanisms to maintain the capacity of ILC2s to produce TH2 cytokines under chronic inflammatory conditions. Here, we report that Runx proteins are essential to prevent exaggerated activation of ILC2, in part by antagonizing GATA-3 function at steady state. However, during allergic inflammation, the absence of Runx in ILC2s impaired their ability to proliferate and produce effector TH2 cytokines and chemokines, but instead induced expression of T cell exhaustion markers including IL-10 and TIGIT. These exhausted ILC2s were unabale to induce type 2 immune responses against repeated allergen inhalation. Thus, Runx proteins protect ILC2s from exhaustion during continuous allergic inflammation.
2019-01-07 | GSE111871 | GEO
Project description:Runx transcription factors play pivotal roles in the development of hematopoietic cells, including T cells. However, the Runx-target genes in early stages of thymic T cell development have been only partially elucidated. Moreover, the relationships of different Runx paralogs, whether they compete or collaborate with each other, are unknown. We have performed CRISPR-Cas9 mediated acute deletion of Runx1 and Runx3, alone and in combination, to define the functions of Runx factors and their target genes. We focused on two distinct stages of early T cell development; before lineage commitment (Phase1) and after commitment (Phase2). Our data suggest that Runx1 and Runx3 are functionally redundant in Phase1, hence the absence of one factor was compensated by the other factor. In Phase2, Runx1 becomes a major contributor, while low levels of Runx3 still strengthened the Runx1-mediated target gene regulation and showed an additive effect. Of importance, we found that Runx1 and Runx3 upregulate T cell programs and inhibit alternative lineage genes. In order to capture the developmental status of Runx-perturbed cells, we performed supervised principal component analysis (PCA) using a fixed frame of PC loadings from single cell RNA-seq analysis of normal in vivo-derived thymocytes. Unlike the reference in vitro and in vivo pro-T cell population or sgControl introduced cells, Runx knockout cells either failed to progress fully (Phase1) or deflected from the normal developmental trajectory (Phase2), suggesting essential roles of Runx factors in early stages of T development. In addition, we analyzed the correlation between stage-specific genomic occupancy of Runx1 and Runx3 (using previously published data for Runx1, GSE103953) and Runx-mediated gene regulation responses at each stage. Interestingly, genes with dynamic, stage-sensitive expression showed a very significant association with phase-specific genomic interactions of Runx factors, and an especially strong correlation with Runx activated target genes. In summary, our data suggest a pivotal role for Runx transcription factors in thymic T cell development by imposing T lineage specification in Phase1 and instructing the lineage-committed progenitor cells to progress through a normal T developmental trajectory.
2020-07-14 | GSE154304 | GEO