A major contributor to cancer mortality is recurrence and subsequent metastatic transformation following therapeutic intervention. In order to develop new treatment modalities or improve the efficacy of current ones it is important to understand the molecular mechanisms that promote therapy-resistance to cancer cells. One pathway that has been demonstrated to therapy resistance is autophagy, a self-digestive process that can eliminate unnecessary or damaged organelles to protect cancer cells from necrosis. Effective targeting of this pathway could lead to the development of new therapies. In our studies, we found that the VEGF-C/NRP-2 axis is involved in the activation of autophagy, which is essential for the survival of cancer cells following chemotherapy treatment. Furthermore, we identified two VEGF-C/NRP-2-regulated genes, LAMP-2 and WDFY-1 that have previously been suggested to participate in autophagy and vesicular trafficking. The upregulation of WDFY-1 upon depleted level of VEGF-C contributed to cytotoxic drug-mediated cell death. Altogether, these data suggest a link between VEGF-C/neuropilin-2 axis and cancer cell survival despite the presence of chemotherapy-induced stress.
Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for treatment resistance.
Cell line
View SamplesSeveral aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is an increasing amount of evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking a dysbiotic gut to cancer development. Yet, the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut, remain to be determined.
High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.
Sex, Age, Specimen part, Treatment
View SamplesCanonical WNT-signaling is essential for placode formation irrespective of appendage type. At sites of placode initiation, Although WNT-signaling occurs in both epithelium and mesenchyme, the site of most intense activity as revealed by the WNT reporter Axin2-LacZ was in a zone just below the epithelial-mesenchymal interface. In ventral foot-skin, this WNT activity peaked at E17.5, concomitant with sweat bud fate commitment, while in dorsal back-skin, it began at E14.5, concomitant with HF fate specification. Overall design: To address whether WNT-signaling within this zone might regionally influence the transcriptional landscape of body-site mesenchymes to support distinct epithelial fates, we transcriptionally profiled the Axin2-positive and Axin2-negative dermal cells following their FACS-purification from E17.5 ventral foot-skin and E14.5 dorsal back-skin
Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesIncreasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with stemness. Of these, miR-125b is dramatically downregulated in early SC-progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC-progenies, tissue balance is reversibly skewed towards stemness at the expense of epidermal, oil-gland and HF differentiation. Using gain-and-loss of function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesIn adult skin, each hair follicle contains a reservoir of stem cells (the bulge), which can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. Here we report new methods that permit their clonal analyses and engraftment and demonstrate the two defining features of stem cells, namely self-renewal and multi-potency. We also show that, within the bulge, there are two distinct populations, one of which maintains basal lamina contact and temporally precedes the other, which is suprabasal and arises only after the start of the first postnatal hair cycle. This spatial distinction endows them with discrete transcriptional programs, but surprisingly, both populations are growth inhibited in the niche but can self-renew in vitro and make epidermis and hair when grafted. These findings suggest that the niche microenvironment imposes intrinsic stemness features without restricting the establishment of epithelial polarity and changes in gene expression.
Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
Specimen part
View SamplesAt mid-log phase (OD600 of 0.5), unique gene expression patterns were observed between these two strains with 3.4% of the transcripts (188/5570) expressed differentially.
A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa.
No sample metadata fields
View SamplesMouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). HFSCs regenerate hair in response to canonical Wnt signalling. We used RNA-seq to unfold genome-wide chromatin landscapes of ß-catenin within the native HFSC-niche. Overall design: ß-catenin control and cKO hair follicle stem cells (HFSCs) at the onset of anagen skins were FACS-purified for RNA-sequcencing. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing. Telogen>anagen activated bulge hair follicle stem cells (HFSCs) were FACS-purified for RNA-sequcencing.
In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators.
No sample metadata fields
View SamplesThrough Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells isolated from high and low antibody responders to measles vaccination, we identified a set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p, miR-199a-3p, miR-103a, and miR-15a/16 cluster) associated with measles-specific antibody response after vaccination. No CD4+ T cell-specific miRNA expression differences between high and low antibody responders were found. DIANA tool was used for gene/target prediction and pathway enrichment analysis and this yielded several biological processes/pathways, including regulation of adherens junction proteins, Fc-receptor signaling pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling pathway/pathways, transcriptional regulation, apoptosis and virus-related processes, that were significantly associated with neutralizing antibody titers after measles vaccination. This study demonstrates that miRNA expression directly or indirectly influences humoral immunity to measles vaccination and suggests that B cell-specific miRNAs may potentially serve as predictive biomarkers of vaccine response. Overall design: Examination of miRNA expression differences in/between purified B and CD4+ T cells of high and low responders to measles vaccination.
Differential miRNA expression in B cells is associated with inter-individual differences in humoral immune response to measles vaccination.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part, Cell line
View Samples