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SRP076029
Mus musculus
423 Downloadable Samples
Illumina HiSeq 2500
Description
Spermatogonial stem cells (SSCs) are critical for maintaining spermatogenesis throughout adult life. Little is known about how SSCs are first generated. Here, we report the identification of a transcription factor—RHOX10—that promotes the initial establishment of SSCs. We were led to this discovery because we found that conditional loss of a large X-linked gene cluster comprised of 33 related homeobox genes, including Rhox10, causes defects predicted if SSCs fail to be generated or maintained. Remarkably, KO of only Rhox10 elicits SSC-related defects indistinguishable from KO of the entire gene cluster. Using a battery of approaches, including single cell-RNAseq analysis, we determined that loss of Rhox10 causes accumulation of undifferentiated germ cells—Pro-spermatogonia (ProSG)—at a time when they normally would form SSCs. The identification of a transcription factor that drives the initial generation of SSCs has potential therapeutic applications for infertility. Overall design: Single cell RNA-seq analysis of ID4-positive testicular cells from Wildtype and Rhox10 knockout mice (Postnatal day 3 and 7)
Publication Title
The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Briefly, the well characterized female hES cell line H9 was allowed to differentiate into a clonally purified mortal splanchnopleuric mesodermal somatic cell line EN13. The EN13 line was subsequently virally reprogrammed back to an induced pluripotent state (we term re-H9) using OCT4, SOX2, KLF4 retroviral vectors creating isogenic lines of hESC, hiPSC and mortal cells. Our results reveal several important differences between embryo-derived H9 and the induced re-H9 stem cells. We find a dysregulation of genes involved in imprinting and altered expression of X-chromosome localized genes in re-H9 cells.
Publication Title
Suppression of the imprinted gene NNAT and X-chromosome gene activation in isogenic human iPS cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 48 Downloadable Samples
- NextSeq 500
Description
Low affinity Tregs are important for controlling autoimmune diabetes. Overall design: High and low affinity Tregs were isolated from the spleen and pancreatic islets of two-TCR retrogenic mice expressing the insulin-specific TCRs 4-8 and 12-4.4m1.
Publication Title
Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Retinoic-acid receptor-related orphan receptor-?t-positive (ROR?t+) innate lymphoid cells (ILCs) produce interleukin (IL)-22 and IL-17, which are critical for protective immunity against enteric pathogens. The molecular mechanism underlying the development and survival of ROR?t+ ILCs is not thoroughly understood. Here we show that Dedicator of cytokinesis 8 (DOCK8), a scaffolding protein involved in cytoskeletal rearrangement and cell migration, is essential for the protective immunity against Citrobacter rodentium. A comparative RNA sequencing-based analysis reveals an impaired induction of antimicrobial peptides in the colon of DOCK8-deficient mice, which correlates with high susceptibility to infection and a very low number of IL-22-producing ROR?t+ ILCs in their GI tract. Furthermore, DOCK8-deficient ROR?t+ ILCs are less responsive to IL-7 mediated signaling, more prone to apoptosis and produce less IL-22 due to a defect in IL-23-mediated STAT3 phosphorylation. Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of ROR?t+ ILCs. Overall design: Control and DOCK8 KO mice were infected with 2X109 CFU of Citrobacter rodentium and day 8 post infection mice were sacrificed and their colons were harvested (n=5) . Total RNA was purified from the infected colons with RNeasy mini kit (Qiagen). RNA sequencing was performed (pooled RNA sample from five mice in each group) at Genomic Core Facility Southwestern Medical Center, University of Texas.
Publication Title
DOCK8 regulates protective immunity by controlling the function and survival of RORγt+ ILCs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The identifcation of alternatively spliced transcript variants specific to particular biological processes in tumours should increase our understanding of cancer. Hypoxia is an important factor in cancer biology and associated splice variants may present new markers to help with planning treatment. A method was developed to analyse alternative splicing in exon array data, using probeset multiplicity to identify genes with changes in expression across their loci, and a combination of the splicing index and a new metric based on the variation of reliability weighted fold changes to detect changes in the splicing patterns. The approach was validated on a cancer/normal sample dataset in which alternative splicing events had been confirmed using RT-PCR. We then analysed ten head and neck squamous cell carcinomas using exon arrays and identified differentially expressed splice variants in five samples with high versus five with low levels of hypoxia-associated genes (Winter et al, 2007; Cancer Res 67:3441-9). The analysis identified a splice variant of LAMA3 (Laminin 3), LAMA3-A, known to be involved in tumour cell invasion and progression. The full-length transcript of the gene (LAMA3-B) did not appear to be hypoxia-associated. The results were confirmed using qualitative real time PCR. In a series of 59 prospectively-collected head and neck tumours (Winter et al, 2007; Cancer Res 67:3441-9), expression of LAMA3-A had prognostic significance whereas LAMA3-B did not. This work illustrates the potential for alternatively spliced transcripts to act as biomarkers of disease prognosis with improved specificity for particular tissues or conditions over assays which do not discriminate between splice variants.
Publication Title
Exon array analysis of head and neck cancers identifies a hypoxia related splice variant of LAMA3 associated with a poor prognosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Publication Title
Prenatal origin of separate evolution of leukemia in identical twins.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Biologic markers of immune tolerance may facilitate tailoring of immune suppression duration after allogeneic hematopoietic cell transplantation (HCT). In a cross-sectional study, peripheral blood samples were obtained from tolerant (n=15, median 38.5 months post-HCT) and non-tolerant (n=17, median 39.5 post-HCT) HCT recipients and healthy control subjects (n=10) for analysis of immune cell subsets and differential gene expression. There were no significant differences in immune subsets across groups. We identified 281 probe sets unique to the tolerant (TOL) group and 122 for non-tolerant (non-TOL). These were enriched for process networks including NK cell cytotoxicity, antigen presentation, lymphocyte proliferation, and cell cycle and apoptosis. Differential gene expression was enriched for CD56, CD66, and CD14 human lineage-specific gene expression. Differential expression of 20 probe sets between groups was sufficient to develop a classifier with > 90% accuracy, correctly classifying 14/15 TOL cases and 15/17 non-TOL cases. These data suggest that differential gene expression can be utilized to accurately classify tolerant patients following HCT. Prospective investigation of immune tolerance biologic markers is warranted.
Publication Title
Tolerance associated gene expression following allogeneic hematopoietic cell transplantation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 9 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Differential gene expression is assessed in substantia nigra and basal ganglia of neurodegenertion with brain iron accumulation cases (BIA) compared to matched normal controls (c).
Publication Title
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human and murine studies showed that granulocyte macrophage colony-stimulating factor (GM-CSF) exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF-activated monocytes (GMaM). We used microarray technology and functional assays to characterize GMaM in vitro and used a mouse model of colitis to study GMaM functions in vivo.
Publication Title
Reprogramming of monocytes by GM-CSF contributes to regulatory immune functions during intestinal inflammation.
Sample Metadata Fields
Specimen part
View Samples