We found that the non-essential amino acid L-Proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells (ESCs) into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic stem cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the transcriptome
L-Proline induces a mesenchymal-like invasive program in embryonic stem cells by remodeling H3K9 and H3K36 methylation.
Cell line
View SamplesSamples 1-4 report RNA-seq transcriptome profiling of the L-Proline- (L-Pro) and bFgf/ActivinA- (F/A) derived mCherry+/eGFP+ (yellow) ESC population, using the Illumina HiSeq platform. Whole-genome expression revealed that more than 1000 genes were significantly deregulated in L-Pro- and F/A-induced cells compared to control (mCherry+/eGFP- red cells) and the two population shared up to 75% of deregulated genes with the same deregulation trend. Specifically, the pluripotency-associated genes were downregulated either at similar level (Nanog, Klf2, Klf4 and Gbx2) or at lower levels (up to 10 times) (Dppa 2, 3, 4, 5a, Rex1, Esrrb) in F/A- compared to L-Pro-treated cells. Interestingly, mesendodermal-related genes (e.g. Brachyury, Cer1, Dkk1, Eomes, Foxa2, and Sox17) were induced in both conditions but at significant higher levels in F/A- compared to L-Pro-treated cells. The transcriptome analysis of mCherry+/eGFP+ (yellow) cells supported the idea that L-Pro mimics F/A in inducing a naïve to primed transition, and suggested that it exerted a milder (weaker) effect. Samples 5-14 report RNA-seq transcriptome profiling of the mir-290_mCherry/mir-302_eGFP dual reporter ESCs (DRESCs) bulk culture, grown in FBS/LIF ± VitaminC (VitC) and L-Proline (L-Pro) and compared them to the standard naive/2i and primed/bFgf/ActivinA-EpiSCs (F/A), using the Illumina HiSeq platform. Whole-genome expression identified around 7900 deregulated genes in the different conditions, (fold change=2 and pvalue<0.05). Principal component analysis (PCA) placed VitC between 2i and untreated control, and L-Pro between control and F/A. Accordingly, a set of pluripotency-associated genes was expressed at higher level in 2i and VitC conditions, while downregulated in L-Pro and F/A, compared to control. Conversely, priming markers were downregulated in 2i and VitC and upregulated in L-Pro and F/A compared to control The transcriptome analysis supported that VitC- and L-Pro captured alternative pluripotency states that can be likely placed between naïve/2i and primed/F/A states. Overall design: RNA-seq profiling of ESCs grown in FBS/LIF ± VitC, 2i, L-Pro or F/A, using the Illumina HiSeq platform
Vitamin C and l-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum.
Cell line, Subject
View SamplesThalidomide-dexamethasone (TD) combination is an effective induction therapy for newly diagnosed multiple myeloma patients, candidates for subsequent autologous stem cell transplantation (ASCT). Since maximization of tumor response before ASCT may favorably affect the clinical outcomes, we designed a study to identify a gene expression profile (GEP) signature predictive of attainment of complete response to TD induction therapy. CD138+ bone marrow samples obtained at diagnosis from 112/311 patients were analyzed. Two subsequent time phases were planned. Firstly, a GEP supervised analysis, performed on a training set of 32 patients, allowed to identify 157 probe sets differentially expressed in complete responder + near complete responder (CR+nCR) versus partial responder patients. Than, we generated an 8-gene GEP signature predicting at diagnosis the probability to achieve CR+nCR to TD induction therapy. The performance of this assay was subsequently validated in an 80 patients training set. The 8-gene signature provide a negative predictive value of 93% and a positive predictive value of 44%. The 8 genes were down-regulated in patients who achieved at least a nCR. These results could be an important first step to adopting a diagnostic assay, used to determine, at diagnosis, patients who will respond more favourably to a particular treatment strategy.
Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide-dexamethasone incorporated into double autologous transplantation.
Age, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Specimen part, Disease, Disease stage, Subject
View SamplesThe prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is an early and deep tumour burden reduction; this characterizes and defines the complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC derived from MM patients who achieved CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.
No sample metadata fields
View SamplesWe hypothesized that the relative abundances of host cell transcripts in lymph nodes of animals with malignant catarrhal fever (MCF), compared to healthy controls, may be used to identify pathways that may help to explain the pathogenesis of MCF. Therefore, an abundance of host cell gene expression patterns in lymph nodes of animals with MCF and healthy controls were analyzed by microarray. Indeed, a vast number of genes related to inflammatory processes, lymphocyte activation, cell proliferation and apoptosis were detected at different abundances. However, the IL-2 transcript was eminent among the transcripts, which were, compared to healthy controls, less abundant in animals with MCF. Compared to healthy cattle, bovines with MCF appear to mimic an IL-2 knockout phenotype that has been described in mice. This supports the hypothesis that immunopathogenic events are linked to the pathogenesis of MCF. IL-2-deficiency may play an important role in the process.
Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.
No sample metadata fields
View SamplesAlthough an important association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago, an active role for the lymphatic system in metastatic dissemination has only recently been examined. We demonstrate that the Six1 homeoprotein promotes peri- and intra-tumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. We identify the pro-lymphangiogenic factor, VEGF-C, as required for this process, and demonstrate transcriptional induction as the mechanism of regulation of VEGF-C expression by Six1. Using a different, but complementary animal model, we show that while required, VEGF-C is not sufficient for the pro-metastatic effects of Six1. Verifying the clinical significance of this pro-metastatic Six1-VEGF-C axis, we demonstrate co-expression of Six1 and VEGF-C in human breast cancer.
SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer.
Specimen part, Cell line
View SamplesRNA-seq libraries purified from the visual cortices of neurons expressing Emx-, GAD2-, PV-, SST-, or VIP-Cre using the Ribotag allele. Seq libraries are provided from mice raised in standard housing, or housed in the dark for two weeks (dark-housed), or dark-housed and then exposed to light for 1, 3, or 7.5 hours. These seq libraries represent the genetic response of distinct types of cortical interneurons to altered sensory experience. Overall design: To explore how sensory experience affects gene expression, we examined this process in the visual cortex of adult mice that were housed in standard conditions, in complete darkness (i.e. dark-housed), or dark-housed and then exposed to light for increasing amounts of time. We generated mice that were heterozygous for alleles of either Emx-,Gad2-,Sst-,Vip- or Pv-Cre, and were also heterozygous for the Rpl22-HA (RiboTag) allele, which expresses an HA-tagged ribosomal protein specifically in Cre-expressing neurons. We performed RNA-Seq on RNA isolated from the dark-housed/light-exposed RiboTag-mice; Experiments were done in 3 biological replicates and the visual cortices of 3 mice were pooled per sample at each time-point and for each Cre line.
Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.
Age, Specimen part, Cell line, Subject
View SamplesThe microarray experiment was employed to evaluate the gene expressions in skin lesions of dermatomyositis and healthy controls.
IL18-containing 5-gene signature distinguishes histologically identical dermatomyositis and lupus erythematosus skin lesions.
Disease, Subject
View Samples