The interaction between cancer and stroma plays a key role in tumor progression. Inactivation of p53 is often observed in stromal cells surrounding in cancer, suggesting that p53 in fibroblasts is involved in tumor progression.
TSPAN12 is a critical factor for cancer-fibroblast cell contact-mediated cancer invasion.
Sex, Specimen part, Cell line
View SamplesHuman pluripotent stem cells (hPSCs) such as embryonic stem cells and induced pluripotent stem cells are promising materials for cell-based regenerative therapies to heart diseases. However, until realization there are many hurdles such as high efficiency of cardiac differentiation of hPSCs and production of clinical-grade cardiac cells derived from hPSCs. Here, we show that a novel small molecule KY02111 robustly enhances differentiation to functional cardiomyocytes from hPSCs.
A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.
Specimen part, Cell line
View SamplesIn lung cancer progression, p53 mutations are more often observed in invasive tumors than in non-invasive tumors, suggesting that p53 is involved in tumor invasion and metastasis. To understand the nature of p53 function as a tumor suppressor, it is crucial to elucidate the detailed mechanism of the alteration in epithelial cells, the main origin of solid tumors, following p53 inactivation.
TSPAN2 is involved in cell invasion and motility during lung cancer progression.
Sex, Age, Specimen part, Treatment
View SamplesOral food intake maintains gastrointestinal cell turnover and impacts the morphology and function of intestinal epithelial cells. However, the underlying mechanism is not fully elucidated, especially in the large intestine. Therefore, we analyzed the colonic epithelial cell turnover in starved and re-fed mice.
Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells.
Specimen part
View SamplesCommensal bacteria shapes gut immune system. Colonization bacteria increase the frequency of regulatory T cells, however, the molecular mechanisms has not yet been unknown. To reveal the mechanism, we isolated Treg cells and Non-Treg cells and performed the global expression analysis.
The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells.
Specimen part
View SamplesWe report transcriptome of Klf9-OE PGC by RNA-seq Overall design: RNA-seq of Klf9-OE clutured for one day in bFGF containing GS medium by using Illumina HiSeq2500.
Identification of KLF9 and BCL3 as transcription factors that enhance reprogramming of primordial germ cells.
Specimen part, Subject
View SamplesClassic ‘position effect’ experiments repositioned genes to the telomere to demonstrate that the epigenetic landscape can dramatically alter gene expression. Here we show that systematic gene knockout collections provide an exceptional resource for interrogating position effects, not only at the telomere but at every single genetic locus. Because deleted genes are replaced by the same reporter gene, interrogation of this reporter provides a sensitive probe into many different chromatin environments while controlling for genetic context. Using this approach we find that, whereas replacement of yeast genes with the kanMX marker does not perturb the chromatin landscape, differences due to gene position account for more than 35% of marker gene activity. We observe chromatin influences different from those reported previously, including an antagonistic interaction between histone H3 lysine 36 trimethylation (H3K36me3) and the Rap1 transcriptional activation site in kanMX that is mediated through a Set2-Rpd3-dependent pathway. This interaction explains why some yeast genes have been resistant to deletion and allows successful generation of these deletion strains using a modified transformation procedure. These findings demonstrate that chromatin regulation is not governed by a uniform ‘histone code’, but by specific interactions between chromatin and genetic factors. Overall design: Data included are RNA-Seq data for 4 heterzygous diploid yeast strains and diploid wild-type. Therea re three replicates for each heterzygous strain, and six replicates for wild-type.
Decoupling epigenetic and genetic effects through systematic analysis of gene position.
Subject
View SamplesGene expression in wild-type and p38a-knockout dendritic cells (DCs) were compared. Lymph node dendritic cells were isolated from mice, and left unstimulated and stimulated with Pam3CSK4, a toll-like receptor 2 agonist.
Cell type-specific targeting dissociates the therapeutic from the adverse effects of protein kinase inhibition in allergic skin disease.
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View SamplesObjective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38-controlled transcripts comprising female- and male-specific gene modules, with greater p38 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS
Sex-specific control of central nervous system autoimmunity by p38 mitogen-activated protein kinase signaling in myeloid cells.
Sex, Specimen part
View Samples