To identify downstream transcription factors induced by retinoic acid, we stimulated SFZ cells with 10 M retinoic acid for 24 hours and performed microarray analysis.
Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5.
Specimen part, Treatment
View SamplesThe Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer element PGSE, which regulates their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway. Overall design: Three control samples (DMSO-treated) and three 4MU-xyloside-treated samples
PGSE Is a Novel Enhancer Regulating the Proteoglycan Pathway of the Mammalian Golgi Stress Response.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Interferon stimulation creates chromatin marks and establishes transcriptional memory.
Specimen part, Time
View Samplesdetermination of gene regulation by sterol and sphingolipid composition
Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology.
Sex
View SamplesTGF-b is an important pleiotropic cytokine with potent immunoregulatory properties. Although many previous reports have been proposed for the immunoregulatory functions of TGF-b on T cells, such as the suppression of cell proliferation, cytokine production and cytokine signaling, as well as the induction of apoptosis, it is not well elucidated whether the each effect of TGF-b on T cells is dependent on Smad signaling or Smad-independent other signaling pathways.
Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development.
Specimen part, Treatment
View SamplesTo elucidate the mechanisms by which Nrf2 regulates cell growth, we performed global gene expression profiling of A549 lung cancer cells with knockdown of Nrf2. Gene networks associated with carbohydrate metabolism and drug metabolism were significantly downregulated in Nrf2-depleted A549 cells. Gene Set Enrichment Analysis revealed significant enrichment of genes associated with carbohydrate catabolic processes, positive regulation of metabolic processes, PPP, and arachidonic acid metabolism. In summary, this analysis revealed that Nrf2 positively regulates transcription of genes that play key roles in central carbon metabolism.
Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis.
Specimen part, Cell line
View SamplesMultipotent and pluripotent stem cells have significant potential as sources for cell replacement therapies. However, the low yield and quality of in vitro differentiated cells produced from various stem cell sources presents a significant limitation for therapeutic applications. The most mature use of these stem cell products is in the field of transfusion medicine, where stem cell-derived red blood cells (RBCs) have clinically-proven potential as alternative transfusion products. To improve upon current approaches for RBC production, we used insight from both common and rare human genetic variation of blood counts to focus on the SH2B3 gene. By producing loss of function of SH2B3 using targeted knockdown and genome editing approaches in human hematopoietic stem and progenitor cells, as well as human pluripotent stem cells, we are able to significantly improve both the quality and yield of in vitro derived RBCs. We illustrate how insight from human genetic variation can assist in the development of broadly applicable approaches that have tremendous value for regenerative medicine.
Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Sex, Specimen part
View SamplesPreimplantation embryos undergo a transient wave of genome-wide demethylation with the exception of imprinted genes that are critical for fetal development. Here we show that the derivation of female mouse embryonic stem cells (ESCs) in the presence of inhibitors of MEK1/2 and Gsk3 (2i-ESCs), known as 2i or ground-state culture conditions, results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. In this study, we analyzed global gene expression profile and global DNA methylation status in 2i-ESCs and 2i-ESCs derived differentiated cells. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Specimen part
View SamplesCo-stimulatory molecules of the CD28 family on T lymphocytes integrate cues from innate immune system sensors, and modulate activation responses in conventional CD4+ T cells (Tconv) and their FoxP3+ regulatory counterparts (Treg). To better understand how costimulatory and co-inhibitory signals might be integrated, we profiled the changes in gene expression elicited in the hours and days after engagement of Treg and Tconv by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BTLA or -CD80.
Convergent and divergent effects of costimulatory molecules in conventional and regulatory CD4+ T cells.
Sex, Age, Specimen part
View Samples