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GSE107385
Homo sapiens
5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
we employed DNA microarray platform to compare the gene expression patterns in primary human cardiomyocytes treated with trastuzumab (50g/ml), trastuzumab (50g/ml) plus pertuzumab (50g/ml), T-DM1 (10 g/ml), or control (no treatment).
Publication Title
Type IIB DNA topoisomerase is downregulated by trastuzumab and doxorubicin to synergize cardiotoxicity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 88 Downloadable Samples
Illumina HiSeq 2000
Description
Here we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. Overall design: mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.
Publication Title
Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tertiary lymphoid organs (TLOs) emerge in response to nonresolving inflammation but their roles in adaptive immunity remain unknown. Here, we explored artery TLOs (ATLOs) to delineate atherosclerosis T cell responses in apoe-/- mice during aging. Though the T cell repertoire showed systemic age-associated contractions in size and modifications in subtype composition and activation, wt and apoe-/- mice were equally affected. In contrast, ATLOs - but not wt aortae, apoe-/- aorta segments without ATLOs or atherosclerotic plaques - promoted T cell recruitment, altered characteristics of T cell motility, primed and imprinted T cells in situ, generated CD4+/FoxP3-, CD4+/FoxP3+, CD8+/FoxP3- effector and central memory cells, and converted nave CD4+/FoxP3- T cells into induced Treg cells. ATLOs also showed substantially increased antigen presentation capability by conventional dendritic cells (DCs) and monocyte-derived DCs but not by plasmacytoid DCs. Thus, the senescent immune system specifically employs ATLOs to control dichotomic atherosclerosis T cell immune responses. We assembled transcriptome maps of wt and apoe-/- aortae and aorta-draining RLNs and identified ATLOs as major sites of atherosclerosis-specific T cell responses during aging: Transcriptome atlases of wt and apoe-/- abdominal aortae and associated draining RLNs were constructed from laser capture microdissection (LCM)-based whole genome mRNA expression microarrays yielding 6 maps: wt adventitia (tissue-1); wt RLN (tissue-2); apoe-/- ATLOs (tissue-3); apoe-/- RLN (tissue-4); apoe-/- adventitia without adjacent plaques (tissue-5), and plaques (tissue-6). Several two-tissue comparisons within the transcriptome atlases are noteworthy: Unexpectedly, transcriptomes of wt and apoe-/- RLNs were virtually identical; additonal data revealed that transcriptomes of RLNs were strikingly similar to those of inguinal LNs which do not drain the aorta adventitia (as shown of India ink injection experiments of surgically exposed aortae); in sharp contrast, wt adventitia versus ATLOs revealed 1405 differentially expressed transcripts many of which encoded members of GO terms immune response and inflammatory response; the ATLO-plaque comparison also showed > 1000 differentially expressed transcripts; however, wt adventitia versus apoe-/- adventitia without plaque showed few genes (< 5 % of differentially expressed transcripts of the wt adventitia-ATLO comparison). Thus, the aorta transcriptome atlases support the conclusion that neither aorta-draining apoe-/- RLNs nor ILNs participate in atherosclerosis-specific T cell responses. In addition, they demonstrate that T cell responses in the diseased aorta are highly territorialized. Finally, these data show that the immune responses carried out in ATLOs differ significantly from those carried out in plaques. We next identified three major clusters within the transcriptome atlases through ANOVA analyses and application of strict filters: An adventitia cluster, a plaque/ATLO cluster, and a LN/plaque cluster. The total number of differentially expressed genes in each cluster were examined for GO terms immune response, inflammatory response, T cell activation, positive regulation of T cell response, and T cell proliferation. Within the adventitia cluster, similarities of transcriptomes of wt adventitia and apoe-/- adventitia without associated plaque versus ATLOs indicate that a robust number of immune response-regulating genes are selectively expressed in ATLOs which are located within a distance of few m of the adventitia without associated plaques indicating a very high degree of territoriality of the atherosclerosis T cell response. Furthermore, unlike the total number of differentially regulated transcripts, the majority of transcripts among GO terms immune response and inflammatory response, was up-regulated. Inspection of the plaque/ATLO cluster provided further information: The majority of immune response regulating genes where expressed at a higher level in ATLOs when compared to plaques though plaques also contained a significant number of immune response regulating genes; the reverse is true for genes regulating inflammation. Finally, the lymph node cluster revealed that though the majority of immune response regulating genes resides in both wt and apoe-/- RLNs (with little differences between them) ATLOs express a selected set of immune response regulating genes at a higher level when compared to LNs. In addition, the inflammatory component of ATLOs when compared to LNs is documented by the finding that many more genes regulating inflammation reside in ATLOs even when compared to those of plaques.
Publication Title
Generation of Aorta Transcript Atlases of Wild-Type and Apolipoprotein E-null Mice by Laser Capture Microdissection-Based mRNA Expression Microarrays.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To understand molecular mechanisms underlying the synergy of Rb loss and E2F8 loss, we used gene expression profiling to assess molecular changes in Mx1-Cre-mediated knockout (KO) mice using RNA isolated from sorted Ter119+CD71high Erythroblasts.
Publication Title
Inactivation of Rb and E2f8 synergizes to trigger stressed DNA replication during erythroid terminal differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
RPS19 mutations are the most common cause of the human disorder Diamond Blackfan Anemia. The R62W mutation was hypothesized to act in a dominant negative fashion and mice expressing RPS19R62W have many of the characteristics of Diamond Blackfan Anemia.
Publication Title
A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NOD mice deficient in the transcription factor Batf3 never develop diabetes. The goal of this study was to determine if NOD.Batf3-/- mice islets had any inflammatory signature associated with type 1 diabetes. Islets of Langerhans were isolated from NOD, NOD.Batf3-/-, and NOD.Rag1-/- and then compared to determine inflammatory gene profiles. At 6 and 8 weeks of age, NOD.Batf3-/- islets had an absence of inflammatory gene expression and were almost identical to uninflamed NOD.Rag1-/- islets. This work shows that absence of the Batf3 transcription factor is sufficient to prevent all the inflammatory sequelae of autoimmune diabetes.
Publication Title
A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In plants, effector-triggered immunity (ETI) is often associated with programmed cell death (PCD). Although the intracellular immune receptors involved in ETI have been studied extensively, how their activation leads to PCD and disease resistance is poorly understood. We found that the Arabidopsis nuclear envelope protein, CPR5 (constitutive expresser of PR genes 5), plays a crucial role in controlling cell fate in response to stress, as the cpr5 mutant exhibits spontaneous cell death and heightened immunity. A genetic screen revealed that the Cip/Kip CKIs (cyclin-dependent kinase inhibitors), SIM (siamese) and SMR1 (siamese-related 1), are essential for CPR5 signaling, as the sim smr1 double mutant fully suppressed the cpr5 phenotype. More significantly, PCD and ETI are compromised in sim smr1 even with the wild-type CPR5.
Publication Title
A noncanonical role for the CKI-RB-E2F cell-cycle signaling pathway in plant effector-triggered immunity.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Identification of AvrRpt2-mediated differential gene expression in Arabidopsis
Publication Title
A noncanonical role for the CKI-RB-E2F cell-cycle signaling pathway in plant effector-triggered immunity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2000
Description
Human erythroblasts purified from cord blood were cultured in vitro and FACS-sorted into five highly purified populations representing distinct differentiation stages: proerythroblasts, early basophilic erythroblasts, late basophilic erythroblasts, polychromatophilic erythroblasts, and orthochromatophilic erythroblasts. The methods for culture and sorting experiments are given in Hu et al. 2013. For each RNA-seq library, RNA was isolated from 1x 106 sorted human erythroblasts using RNeasy Plus Mini kits (Qiagen). Libraries were then prepared using Illumina TruSeqTM RNA kits to obtain 50 nt reads. Collaborators at the New Your Blood Center were responsible for erythroblast culture, FACS purification of erythroblast populations, and acquisition of RNA-seq data. Collaborators at U.C. Berkeley and Lawrence Berkeley National Laboratory performed data analysis and experimental validation of alternative splicing in erythroblasts. Results: Differentiating erythroblasts execute a dynamic alternative splicing program that is enriched in genes affecting cell cycle, organelle organization, chromatin function, and RNA processing. Alternative splicing plays a major role in regulating gene expression to ensure synthesis of appropriate proteome at each stage as the cells remodel in preparation for production of mature red cells. Overall design: Erythroid differentiation stage-specific transcriptome analysis was performed by RNA-seq analysis of highly purified erythroblast populations
Publication Title
A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2500, NextSeq 500
Description
Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition. Overall design: polyA mRNA -seq in conditions with the indicated knockdown treatments
Publication Title
Promoter-proximal pausing mediated by the exon junction complex regulates splicing.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples