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GSE22224
Homo sapiens
44 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4+CD25highFoxp3+ T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.
Publication Title
Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development. Overall design: Time course RNA-Seq analysis H1 ESCs differentiated into endothelial cells
Publication Title
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development.
Publication Title
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Nephron progenitor cells generate nephrons, the basic units of kidney. We developed methods to culture mouse and human NPCs in their self-renewal state in vitro with full nephrogenic potentials. The RNA-seq here is used to compare the global gene expression of long-term cultured mouse NPCs and their cognate freshly isolated primary NPCs Methods: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line). To generate rpkm values from raw data, single-end 50bp reads were mapped to the UCSC mouse transcriptome (mm9) by STAR9, allowing for up to 10 mismatches (which is the default by STAR). Only the reads aligned uniquely to one genomic location were retained for subsequent analysis. And expression levels of all genes were estimated by Cufflink10 using only the reads with exact matches. Results: The gene expression levels of the "NPC-signature genes" were firstly transformed as logarithm scales. And then the program “prcomp”, a built-in program for principal component analysis in R packages, was employed with default parameters. We evaluated the variance percentage of each principal component, and found the top 3 components accounted for 84.1% of the total variance, where PC1 accounted for 46.42%, PC2 23.87% and PC3 13.81%. Those three PCs are therefore selected as candidate principal components in the further analysis. Another program “scatterplot3d” in the R packages was used to plot the 3D view of PCA, and “ggplot2” was used in 2D view of PCA. The PCA results indicate that cultured NPCs cluster together in PCA analysis while primary NPCs segregate into early (E11.5 to E13.5) and later (E16.5, P1) NPC groups. Interestingly, cultured NPCs are close to early NPCs in both PC1 and PC2 axes, suggesting that cultured NPCs are maintained in state close to early NPCs. The close cluster of P20 and P80 NPCs show the robustness of our culture condition in maintaining stable self-renewal state of NPCs. Conclusions: Our study represents the first analysis comparing the long-term cultured NPC lines we geneated with primary NPCs, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line)
Publication Title
3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Heart failure is a leading cause of mortality and morbidity in the developed world, partly because mammals lack the ability to regenerate heart tissue. Whether this is due to evolutionary loss of regenerative mechanisms present in other organisms or to an inability to activate such mechanisms is currently unclear. Here, we decipher mechanisms underlying heart regeneration in adult zebrafish and show that the molecular regulators of this response are conserved in mammals. We identified miR-99/100 and Let-7a/c, and their protein targets smarca5 and fntb, as critical regulators of cardiomyocyte dedifferentiation and heart regeneration in zebrafish. Although human and murine adult cardiomyocytes fail to elicit an endogenous regenerative response following myocardial infarction, we show that in vivo manipulation of this molecular machinery in mice results in cardiomyocyte dedifferentiation and improved heart functionality after injury. These data provide a proof-of-concept for identifying and activating conserved molecular programs to regenerate the damaged heart. Overall design: RNA-Seq expression profiles of rat cardiomyocytes after knockdown of miR-99/100 and Let-7 miRNAs
Publication Title
In vivo activation of a conserved microRNA program induces mammalian heart regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Mus musculus, Pan troglodytes, Homo sapiens
- 11 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An alternative pluripotent state confers interspecies chimaeric competency.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Here we show that by simple modulation of extrinsic signaling pathways, a new class of pluripotent stem cells, referred to as intrinsic state-epiblast stem cells (IS-EPIs), could be efficiently derived from different stages of the early embryo. IS-EPIs share features of primed pluripotency yet are distinct from EpiSCs in their molecular characteristics and ability to colonize post-implantation embryos. We performed Microarray analysis and compared global gene expression pattern among amplified RNA samples from ESCs, EpiSCS, IS-EPIs as well as in vivo isolated Epiblasts.
Publication Title
An alternative pluripotent state confers interspecies chimaeric competency.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Cancer originates as the progressive accumulation of genetic mutations in proto-oncogenes and tumor suppressors. However, the early events underlying tumor initiation remain largely elusive, mostly due to the general lack of information regarding the cells-of-origin responsible for tumor formation as well as the precise impacts of genetic insults on tumor initiation in vivo. Here, we demonstrate that Sox2-positive (Sox2+) adult stem cells are responsible for epithelial squamous tumor formation. Conditional expression of oncogenic Kras (KrasG12D) and knockout of p53 (also known as Trp53) in Sox2+ cells quickly and specifically resulted in the formation of squamous tumors in the forestomach and esophagus. GFP-based lineage tracing experiments demonstrated that Sox2+ cells are the cells-of-origin of squamous tumors in the esophagus and forestomach. Of note, our data showed that p53 deletion alone did not suffice for tumor initiation. On the contrary, tumor initiation was observed upon KrasG12D activation whereas p53 deletion further contributed to the malignancy of the generated tumors, pointing out distinct roles for Kras activation and p53 deletion in squamous tumor formation and progression, to which a multihit carcinogenesis model can be applied. Global gene expression analysis revealed secreting factors upregulated in the generated tumors induced by oncogenic Kras, which contribute to tumor progression. Taken together, these results demonstrate that epithelial squamous tumors can specifically originate as a consequence of defined genetic mutations in a Sox2+ cell population and highlight the connections between proliferative stem cells and tumor development in vivo. Overall design: Expression profiling of mouse tissues with genetically induced tumors by RNA-Seq
Publication Title
Mutations in foregut SOX2<sup>+</sup> cells induce efficient proliferation via CXCR2 pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Triple-negative (TN) breast cancers need to be refined in order to identify therapeutic subgroups of patients.
Publication Title
Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response.
Sample Metadata Fields
Disease
View Samples