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GSE65111
Saccharomyces cerevisiae
8 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
In Saccharomyces cerevisiae, the maturation of both pre-rRNA and pre-small nucleolar RNAs (pre-snoRNAs) involves common factors, thereby providing a potential mechanism for the coregulation of snoRNA and rRNA synthesis. In this study, we examined the global impact of the double-stranded-RNA-specific RNase Rnt1p, which is required for pre-rRNA processing, on the maturation of all known snoRNAs. In silico searches for Rnt1p cleavage signals, and genome-wide analysis of the Rnt1p-dependent expression profile, identified seven new Rnt1p substrates. Interestingly, two of the newly identified Rnt1p-dependent snoRNAs, snR39 and snR59, are located in the introns of the ribosomal protein genes RPL7A and RPL7B. In vitro and in vivo experiments indicated that snR39 is normally processed from the lariat of RPL7A, suggesting that the expressions of RPL7A and snR39 are linked. In contrast, snR59 is produced by a direct cleavage of the RPL7B pre-mRNA, indicating that a single pre-mRNA transcript cannot be spliced to produce a mature RPL7B mRNA and processed by Rnt1p to produce a mature snR59 simultaneously. The results presented here reveal a new role of yeast RNase III in the processing of intron-encoded snoRNAs that permits independent regulation of the host mRNA and its associated snoRNA.
Publication Title
Genome-wide prediction and analysis of yeast RNase III-dependent snoRNA processing signals.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
Illumina HiSeq 2500
Description
Precise regulation of stem cell self-renewal and differentiation properties is essential for tissue homeostasis. Using the adult Drosophila intestine to study molecular mechanisms controlling stem cell properties, we identify the gene split-ends (spen) in a genetic screen as a novel regulator of intestinal stem cell fate. Spen family genes encode conserved RNA recognition motif-containing proteins that are reported to have roles in RNA splicing and transcriptional regulation. We demonstrate that spen loss of function in intestinal stem cells results in an abnormal increase in the number of stem cell-like cells and that Spen acts to control early commitment events of the stem cells. Using two-color cell sorting of stem cells and their daughters, we characterize spen-dependent changes in RNA abundance and exon usage, and find potential key regulators downstream of spen. Our work identifies spen as an important regulator of adult stem cells in the Drosophila intestine, provides new insight to Spen-family protein functions, and may also shed light on Spen's mode of action in other developmental contexts. Overall design: Three biological replicates were sequenced per each 4 conditions
Publication Title
Spen limits intestinal stem cell self-renewal.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 189 Downloadable Samples
Description
Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic lamina propria mesenchymal cells from 3 healthy donors. 183 single cell libraries, 6 bulk controls, 3 empty well controls. Individual donors processed as separate batches with Fluidigm C1 IFCs and pooled for sequencing (2 x Illumina HiSeq 2500 lanes).
Publication Title
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 162 Downloadable Samples
- Illumina HiSeq 4000
Description
Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Ulcerative colitis colonic lamina propria mesenchymal cells from 3 donors. 178 single cell libraries, 7 bulk controls, 7 empty well controls. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 4000 lane).
Publication Title
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 89 Downloadable Samples
- Illumina HiSeq 2500
Description
Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic epithelial cells from 3 healthy donors. 92 single cell libraries, 3 bulk controls, 1 empty well control. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 2500 lane).
Publication Title
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Sample Metadata Fields
Disease, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Type 1 diabetes is a multigenic disease caused by T-cell mediated destruction of the insulin producing -cells. Although conventional (targeted) approaches of identifying causative genes have advanced our knowledge of this disease, many questions remain unanswered. Using a whole molecular systems study, we unraveled the genes/molecular pathways that are altered in CD4 T-cells from young NOD mice prior to insulitis (lymphocytic infiltration into the pancreas). Many of the CD4 T-cell altered genes lie within known diabetes susceptibility regions (Idd), including several genes in the diabetes resistance region Idd13 and two genes (Khdrbs1 and Ptp4a2) in the CD4 T-cell diabetogenic activity region Idd9/11. Alterations involved apoptosis/cell proliferation and metabolic pathways (predominant at 2 weeks), inflammation and cell signaling/activation (predominant at 3 weeks), and innate and adaptive immune responses (predominant at 4 weeks). We identified several factors that may regulate these abnormalities: IRF-1, HNF4A, TP53, BCL2L1 (lies within Idd13), IFNG, IL4, IL15, and prostaglandin E2, which were common to all 3 ages; AR and IL6 to 2 and 4 weeks; and Interferon (IFN-I) and IRF-7 to 3 and 4 weeks. Others were unique to the various ages (e. g. MYC, JUN, and APP to 2 weeks; TNF, TGFB1, NFKB, ERK, and p38MAPK to 3 weeks; and IL12 and STAT4 to 4 weeks). Our data suggest that diabetes resistance genes in Idd13 and Idd9/11, and BCL2L1, IL6-AR and IFNG-IRF-1-IFN-I/IRF-7-IL12 pathways play an important role in CD4 T-cells in the early pathogenesis of autoimmune diabetes. Thus, the alternative approach of investigation at the molecular systems level has captured new information, which combined with validation studies, offers the opportunity to test hypotheses on the role played by the genes/molecular pathways identified in this study, to understand better the mechanisms of autoimmune diabetes in CD4 T-cells, and to develop new therapeutic strategies for the disease.
Publication Title
Molecular pathway alterations in CD4 T-cells of nonobese diabetic (NOD) mice in the preinsulitis phase of autoimmune diabetes.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Islet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse a model for human type 1 diabetes (T1DM). The molecular events leading to insulitis are poorly understood. Since TIDM is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease.
Publication Title
Molecular phenotyping of immune cells from young NOD mice reveals abnormal metabolic pathways in the early induction phase of autoimmune diabetes.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 27 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Hypoxia plays a key pathogenic role in the outcome of many pathologic conditions. To elucidate how organisms successfully adapt to hypoxia, a population of Drosophila melanogaster was generated, through an iterative selection process, that is able to complete its lifecycle at 4% O2, a level lethal to the starting parental population. Transcriptomic analysis of flies adapted for >200 generations was performed to identify pathways and processes that contribute to the adapted phenotype, comparing gene expression of three developmental stages with generation-matched control flies. A third group was included, hypoxia-adapted flies reverted to 21% O2 for five generations, to address the relative contributions of genetics and hypoxic environment to the gene expression differences. We identified the largest number of expression differences in 0.5-3 hr post-eclosion adult flies that were hypoxia-adapted and maintained in 4% O2, and found evidence that changes in Wnt signaling contribute to hypoxia tolerance in flies.
Publication Title
Wnt pathway activation increases hypoxia tolerance during development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Cerebellar development requires regulated proliferation of cerebellar granule neuron progenitors (CGNPs). Inadequate CGNP proliferation causes cerebellar hypoplasia while excessive CGNP proliferation can cause medulloblastoma, the most common malignant pediatric brain tumor. Although Sonic Hedgehog (SHH) signaling is known to activate CGNP proliferation, the mechanisms down-regulating proliferation are less defined. We investigated CGNP regulation by GSK-3, which down-regulates proliferation in the forebrain, gut and breast by suppressing mitogenic WNT signaling. In striking contrast, we found that co-deleting Gsk-3α and Gsk-3β blocked CGNP proliferation, causing severe cerebellar hypoplasia. Transcriptomic analysis showed activated WNT signaling and up-regulated Cdkn1a in Gsk-3-deleted CGNPs. These data show that a GSK-3/WNT axis modulates the developmental proliferation of CGNPs and the pathologic growth of SHH-driven medulloblastoma. The requirement for GSK-3 in SHH-driven proliferation suggests that GSK-3 may be targeted for SHH-driven medulloblastoma therapy.
Publication Title
GSK-3 modulates SHH-driven proliferation in postnatal cerebellar neurogenesis and medulloblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The molecular etiology of invididual differences in complex behavior traits and susceptibility to psychiatric illness remains incomplete. Using an unbiased genetic approach in a mouse model, Quantitative Trait Loci (QTL) influencing anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10 and an interval specific congenic strain (ISCS; A.B6chr10; 66 cM to telomere) was developed. This A.B6chr10 strain facilitated defining the behavioral influences of this region as well as gene expression profiling to identify candidate gene(s) underlying this QTL. By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41 / Neuregulin Receptor Degrading Protein1; Nrdp1) was differentially expressed in the region of interest, comparing the hippocampi of A/J vs A.B6chr10 mice as well as A/J vs B6 mice. By RT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. In addition, protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Among LxS recombinant inbred mice (N=33), Rnf41 hippocampal mRNA expression levels were significantly correlated with open field behavior (r= .454, p=.0073). Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmanns Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls. Overall, Rnf41 is a pleiotropic candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners provide novel etiological pathways for influencing behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness.
Publication Title
An E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41, is a candidate gene for anxiety-like behavior and beta-carboline-induced seizures.
Sample Metadata Fields
No sample metadata fields
View Samples