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SRP125891
Mus musculus
24 Downloadable Samples
NextSeq 500
Description
Purpose: Cortical thymic epithelial cells (cTECs) contain a unique type of proteasomes, thymoproteasomes. Indirect evidence suggests that the key role of PSMB11, a catalytic subunit of thymoproteasomes specific to cTECs, is to generate a unique repertoire of MHC I peptides. Notably, PSMB11-deficient mice display defective development of CD8 thymocytes. The objective of this study was to characterize the impact of PSMB11 on cTECs and thymocyte development. Since different types of proteasomes have non-redundant effects on gene expression, we hypothesized that thymoproteasomes should have a distinct impact on the transcriptome and thereby the function of cTECs. Results: We report that PSMB11 in cortical thymic epithelial cells has dramatic effects on cTECs on both CD4 and CD8 thymocyte populations. PSMB11 modulates the expression of 850 genes in cTECs, 582 in CD4 thymocytes and 284 in CD8 thymocytes. PSMB11-regulated cTEC genes are involved mainly in cell-cell adhesion, extracellular matric organization and thymocyte chemotaxis. PSMB11-deficient cTECs acquire features of mTECs and perturb thymocyte development. Deletion of PSMB11 causes a major cell stress in both CD4 and CD8 thymocyte populations. Of note, PSMB11-deficiency had no impact on medullary thymic epithelial cells (mTECs), which originate from progenitors that express PSMB11 early in ontogeny. Conclusion: We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs. Overall design: We performed RNA-sequencing in triplicate on cTECs, mTECs, and SM, M1 and M2 thymocytes from the CD4 and CD8 lineages, in order to identify differential gene expression between WT and Psmb11-deficient mice.
Publication Title
PSMB11 Orchestrates the Development of CD4 and CD8 Thymocytes via Regulation of Gene Expression in Cortical Thymic Epithelial Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
Affymetrix Murine 11K SubA Array (mu11ksuba)
Description
ab and gd T cells originate from a common, multi-potential precursor population in the thymus, but the molecular mechanisms regulating this lineage fate decision process are unknown. We have identified Sox13 as a gd-specific gene in the immune system. Using Sox13 transgenic mice, we show that SOX13 promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells, but not ab T cells. One mechanism of SOX13 function is the inhibition of WNT/TCF signaling, suggesting that differential WNT/TCF activity is an essential parameter for this binary cell fate choice.
Publication Title
Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The liver has inherent regenerative capacity via mitotic division of mature hepatocytes. However, if the hepatic loss is massive or mature hepatocyte proliferation is impaired by chronic liver injury, HSPC are activated to support liver regeneration. Access to liver tissue from 4 patients who underwent liver transplantation for hepatitis B virus (HBV)- associated acute liver failure (ALF) provided us with the opportunity to investigate the molecular mechanisms of liver regeneration in humans by means of gene expression profiling and immunohistochemistry (IHC). Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual liver specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two-well defined clusters that segregated according to the histopathological severity, i.e. massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong hepatic stem/progenitor cell (HSPC) gene signature, as also confirmed by IHC, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of cancer stem cell genes (EpCAM, CK19 and CK7), whereas the most upregulated genes in SHN were related to cellular growth and proliferation (AKR1B10, NQO1, RRM2, SFN, TOP2A, CCNB1, CDC20, ANLN and KI67). The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound healing process. Conclusion: Our data provide evidence of marked HSPC cell activation and fibrogenesis in HBV-associated ALF, which positively correlate with the extent of liver necrosis. Moreover, we detected a strong tumorigenesis gene signature in ALF, which underlines the relationship between liver regeneration and liver cancer.
Publication Title
Liver regeneration signature in hepatitis B virus (HBV)-associated acute liver failure identified by gene expression profiling.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Inflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control.
Publication Title
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression in intact and hypophysectomized adult mouse liver was assayed by RNA-seq analysis of total liver RNA, as part of a study of growth hormone regulation of hepatic lincRNAs. Overall design: Eight independent pools: two intact males, two intact females, two hypophysectomized males and two hypophysectomized females, comprised of total RNA isolated from 3-5 individual livers / pool, were prepared and used for unstranded RNA-seq.
Publication Title
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Gene expression in adult male mouse liver was assayed by nuclear RNA-seq, as part of a study of hepatic lincRNAs. Overall design: Three independent pools, comprised of nuclear RNA isolated from 4 individual male livers per pool, were prepared and used for RNA-seq.
Publication Title
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression in adult female mouse liver was assayed by nuclear RNA-seq, as part of a study of hepatic lincRNAs. Overall design: Three independent pools, comprised of nuclear RNA isolated from 4 individual livers per pool, were prepared and used for unstranded RNA-seq.
Publication Title
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Gene expression in adult male and female mouse liver was assayed by RNA-seq, as part of a study on hepatic lincRNAs. Overall design: Total liver RNA was prepared from 12 individual male and 12 individual female mice. Four independent pools, comprised of RNA isolated from 6 individual male or female livers (2 pooled biological replicates for each sex) were then prepared and used for RNA-seq.
Publication Title
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression in adult male and female mouse liver was assayed by RNA-seq, as part of a study on chromatin states in male and female mouse and their role in sex-biased liver gene expression (A Sugathan and DJ Waxman (2013) Mol Cell Biol. 33:3594-3610. doi: 10.1128/MCB.00280-13). Overall design: Total liver RNA was prepared from 12 individual male and 12 individual female mice. Four RNA pools, comprised of RNA isolated from 6 individual male or female livers (2 pooled biological replicates for each sex) were then prepared and used for RNA-seq.
Publication Title
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression in adult male and female mouse liver was analyzed based on nuclear RNA-seq, as part of a study on hepatic lincRNAs. Overall design: Nuclear liver RNA was prepared from 6 individual male and 6 individual female mice. Pools comprised of RNA isolated from 6 individual male or female livers (1 pool of 6 biological replicates for each sex) were then prepared and used for strand-specific RNA-seq.
Publication Title
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sample Metadata Fields
No sample metadata fields
View Samples