Cytotoxic T cells confer a prognostic benefit in many tumors, including ovarian cancer. We and others have previously identified a subset of CD8+ T cells, namely CD103+CD8+ T cells, that seems to have a better prognostic effect. The aim of this study is to identify how these CD103+ T cells differ from CD103-CD8+ T cells on mRNA level in human samples of ovarian cancer. Overall design: mRNA profiles of 10 pools of 20 cells CD103+CD8+, 10 pools of 20 cells CD103-CD8+, 20 single-cells CD103+CD8+, 20 single-cells CD103-CD8+ were generated from TILs of 3 ovarian cancers (high-grade serous ovarian cancer) by SMARTseq2
A Transcriptionally Distinct CXCL13<sup>+</sup>CD103<sup>+</sup>CD8<sup>+</sup> T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer.
Subject
View SamplesThe aim of this study was to employ a systems-level analysis to elucidate gene expression networks operating in the CD4 T-cell responses which underpin human atopic disease.
A network modeling approach to analysis of the Th2 memory responses underlying human atopic disease.
Time
View SamplesThe aim of this experiment is to test the ability of the ortholog of Arabidopsis LFY gene from Leanworthia crassa (Lcr) to complement an Arabidopsis LFY mutant. Plants used are homozygous lfy6 mutants (EMS alleles) in Ler background which are transformed or not (for the lfy6 mutant) by genomic clones for Arabidopsis LFY (AthLFY) or Leanworthia crassa LFY (LcrLFY). Flowering was synchronized by growing plants in SD then shifting them to LD. 2 time points samples (wild type Ler) were taken at the end of the SD period as a reference for genes induced by shifting to LD, irrespective of the status at the LFY locus.
Evolutionary divergence of LFY function in the mustards Arabidopsis thaliana and Leavenworthia crassa.
Age, Specimen part, Time
View SamplesMicroarray technology has had a profound impact on gene expression research. Some studies have questioned whether similar expression results are obtained when the same RNA samples are analyzed on different platforms.
The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.
No sample metadata fields
View SamplesThe discovery of genetic variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula- interpeduncular axis as a critical relay circuit in the control of nicotine addiction
Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons.
Specimen part, Disease
View SamplesDespite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling performed on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of 6 chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative RT-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be upregulated on human CD8+ effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8+ effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8+ effector T cells when implanted as xenografts in NOD/scid mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8+ T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of anti-tumor immunity.
Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment.
No sample metadata fields
View SamplesRegulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote their growth and progression. TCF3 (also known as TCF7L1) is a member of the TCF/LEF transcription factor family that is central in regulating epidermal and embryonic stem (ES) cell identity. We found that TCF3 is highly expressed in poorly differentiated human breast cancers, preferentially of the basal-like subtype. This suggested that TCF3 is involved in the regulation of breast cancer cell differentiation state and tumorigenicity. Silencing of TCF3 dramatically decreased the ability of breast cancer cells to initiate tumor formation, and led to decreased tumor growth rates. In culture, TCF3 promotes the sphere formation capacity of breast cancer cells and their self-renewal. We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells, while repressing another distinct target subset. In the normal mouse mammary gland Tcf3 is highly expressed in terminal end buds, structures that lead duct development. Primary mammary cells are dependent on Tcf3 for mammosphere formation, and its overexpression in the developing gland disrupts ductal growth. Our results identify TCF3 as a central regulator of tumor growth and initiation, and a novel link between stem cells and cancer.
Control of breast cancer growth and initiation by the stem cell-associated transcription factor TCF3.
Cell line, Treatment
View SamplesRecent small RNA sequencing data has uncovered extensive modification of the 3’ end of mature microRNAs (miRNAs). This non-templated nucleotide addition can impact miRNA gene regulatory networks through the control of miRNA stability or by interfering with the repression of target mRNAs. The miRNA modifying enzymes responsible for this regulation remain largely uncharacterized. Here we describe the ability for two related terminal uridyl transferases (TUTases), Zcchc6 (TUT7) and Zcchc11 (TUT4), to 3’ mono-uridylate a specific subset of miRNAs involved in cell differentiation and Hox gene control. Zcchc6/11 selectively uridylate these miRNAs in vitro, and we biochemically define a bipartite sequence motif that is necessary and sufficient to confer Zcchc6/11 catalyzed uridylation. Depletion of these TUTases in cultured cells causes the selective loss of 3’ mono-uridylation of many of the same miRNAs. Interestingly, upon TUTase dependent loss of uridylation we observe a concomitant increase in non-templated 3’ mono-adenylation. Our results uncover the molecular basis for sequence specific miRNA mono-uridylation by Zcchc6/11, highlight the precise control of different 3’ miRNA modifications in cells, and have implications for miRNA regulation during development. Overall design: small RNA profiles in TUTases knock-down and control HeLa cells were generated by Illumina deep sequencing
Selective microRNA uridylation by Zcchc6 (TUT7) and Zcchc11 (TUT4).
No sample metadata fields
View SamplesIn utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in adulthood.
In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice.
Sex, Age, Specimen part, Treatment
View SamplesCerebellum from post-natal day 11 L1 knockout mice on the 129Sv background were compared to wild type littermates. The original goal of the study was to determine if there was compensation from other L1 family members or alterations in cell survival or apoptosis. Interestingly no major changes were detected in those families or pathways.
A modifier locus on chromosome 5 contributes to L1 cell adhesion molecule X-linked hydrocephalus in mice.
Sex
View Samples