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Homo sapiens
3 Downloadable Samples
IlluminaHiSeq2000
Description
When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms'' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. Overall design: Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.
Publication Title
Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.
Publication Title
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Cancer stem cell (CSC) identification relies on transplantation assays of cell sub-populations sorted from fresh tumor samples. Herein, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in-vivo propagating patient derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of EMT, invasion/motility, metastasis and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers. Overall design: Tumorigenic fractions from early-passaged PDX
Publication Title
In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1 knockout mice displayed phenotypes similar to those observed on ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes. Overall design: Total RNA-seq from dissected regions of the digestive tract, from wild-type and percc1-/- mice.
Publication Title
Noncoding deletions reveal a gene that is critical for intestinal function.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [HuEx10stv2_Hs_ENST_14.1.0 (huex10st)
Description
Cultures of primary human airway epithelial cells (HAE cells) were exposed to an MDCK equivalent MOI of 0.01 of several swine- and human-origin influenza viruses and RNA was extracted at the 12, 16, and 24 hours post infection.
Publication Title
25-Hydroxycholesterol acts as an amplifier of inflammatory signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Dyskeratosis congenita is a bone marrow failure syndrome characterized by the presence of short telomeres at presentation. The X-linked form is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for in the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, suggesting induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. Here we show that in iPS cells with DKC1 mutations Q31E, A353V and L37 telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin varies, with recurrent mutation A353V showing the most severe effect on telomere maintenance. A353V cells but not Q31E or L37 cells, are refractory to correction by incorporation of a single copy of a wild type DKC1 cDNA into the AAVS1 safe harbor locus. None of the mutant cells show decreased pseudouridine levels in rRNA or defective rRNA processing. Finally transcriptome analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis.
Publication Title
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
A set of changes is identified in the transcription profile associated with the long-term, but not the acute, response to radiation exposure. The study was performed in vivo using zebrafish.
Publication Title
Long-term effects of ionizing radiation on gene expression in a zebrafish model.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples
GSE36527- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Thymic-derived natural T regulatory cells (nTregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs have been shown to express Klrg1, but it remains unclear the extent Klrg1 defines a unique Treg subset. Here we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1- Tregs. This subset is a recent antigen-responsive and a highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving antigen-activated conventional T lymphocytes also operates for Tregs.
Publication Title
IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of nucleus accumbens shell samples from RAR-null mutant mice and their wild type littermates
Publication Title
Genome-wide Analysis of RARβ Transcriptional Targets in Mouse Striatum Links Retinoic Acid Signaling with Huntington's Disease and Other Neurodegenerative Disorders.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Two biological replicate experiments were performed to estimate the bias of the gene expression pattern of infected and non-infected HEp-2 cells. Microarrays hybridized with RNA from 2 h of non-infected HEp-2 cells were used as reference chips for the comparison with microarrays hybridized with RNA from 2 h and 4 h of eukaryotic cells exposed to wt-bacteria and .fasX-mutant. As a reference for chips hybridized with RNA prepared from 6 h p. i. and 8 h p. i. of both GAS-infected HEp-2 cells we used chips that were hybridized with RNA isolated from non-infected cells 8 h p. i. We also compared the microarray data from 2 h of non-infected HEp-2 cells with those from 8 h of non-infected HEp-2 cells to determine the influence of the extended culture on the non-infected cells. Only such genes which were differentially regulated after infection with wt-bacteria and .fasX-mutant infected cells and not differentially present in unequal amounts between the 2 h and 8 h of controls were included in the subsequent statistical analysis.
Publication Title
Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness.
Sample Metadata Fields
Disease, Disease stage, Cell line, Time
View Samples