Few families of signaling factors have been implicated in the control of development. Here we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin and both peptides regulate Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals, but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, pre-dating a complex nervous system.
Neuropeptides: developmental signals in placode progenitor formation.
Specimen part
View SamplesTotal RNA-sequencing on 150-200 ICOS+CD38+ cTfh cells per person prior to vaccination (day 0), and seven (day 63) and 28 (day 84) days after the third vaccination. Overall design: Blood samples were taken from healthy volunteers taking part in a Phase 1b clinical trial. mRNA was isolated from flow sorted circulating Tfh cells (CD4+CD45RA-CXCR5+PD1+ICOS+CD38+ cells) and RNA-sequencing performed on cTfh from days 0, 7 and 28 reletive to vaccination
The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes.
Specimen part, Subject
View SamplesTotal mRNA-sequencing on memory T helper cell populations from human blood and lymph nodes. Overall design: Paired blood and lymph node samples were taken from patients recruited from the renal transplant live donor program at Cambridge University Hospitals NHS Foundation Trust, and who provided informed consent. All patients were either receiving or within 6 months of requiring renal replacement therapy. Patients taking immunosuppressive medication prior to transplant were excluded. mRNA was isolated from flow sorted CD4+ T cell populations and RNA-sequencing performed.
The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes.
Specimen part, Subject
View SamplesA subset of GC B cells that have stopped cycling, upregulated CD38 and downregulated BCL-6 is functionally verified as GC-derived memory B cell precursors (GC-MPs). RNA-seq analyses of the transcriptome were used to probe the developmental trajectory of these cells and their responses to IL-9, a cytokine that is found to drive the memory development from the GC. Overall design: Differential gene expression analyses between GC-MP cells and regular GC B cells in G1 phase (GC-MPP cells); Gene expression profiling of different GC subsets in comparison to memory B cells and plasma cells; acute effects of in vivo IL-9 or anti-IL-9 treatment on GC-MP or GC-MPP cells.
Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells.
Specimen part, Cell line, Treatment, Subject
View SamplesImmune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves but in some it becomes chronic. To investigate whether the two forms of the disease are similar or separate entities we performed DNA microarray analysis of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the expression files between the two forms of the disease. Furthermore, the gene expression of several cytokines differed between the two forms of the disease. This was also reflected in plasma with increased levels of IL-16 and TWEAK and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that the two forms of the disease may be separate entities.
Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sex, Age, Specimen part, Disease
View SamplesDifferential gene expression is assessed in substantia nigra and basal ganglia of neurodegenertion with brain iron accumulation cases (BIA) compared to matched normal controls (c).
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sex, Age, Specimen part, Disease
View SamplesClear cell renal cell carcinoma (ccRCC), the major histotype of cancer derived from kidney, is lack of robust prognostic and/or predictive biomarker and powerful therapeutic target. We previously identified that follistatin-like protein 1 (FSTL1) was significantly down-regulated in ccRCC at the transcription level. In the present study, we characterized, for the first time, that FSTL1 immunostaining was selectively positive in the cytoplasm of distal convoluted tubules. The expression of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P<0.001), as measured using immunohistochemistry in 69 patients with paired specimens, and lower in most ccRCC cell lines than in human embryonic kidney cells, as measured by quantitative RT-PCR. Multivariate Cox regression analysis in 89 patients with follow-up data showed that FSTL1 expression in tumors conferred a favorable postoperative prognosis independently, with a hazard ratio of 0.325 (95% confidence interval: 0.118-0.894). FSTL1 knockdown promoted anchorage independent growth, mobility, and invasion of ccRCC cell lines and promoted cell cycle from G0/G1 phases into S phase; while over-expression of FSTL1 significantly attenuated cell migration ability in ACHN cells. FSTL1 knockdown resulted in decreased expression of E-cadherin and increased expression of N-cadherin in ccRCC cell lines significantly, indicating that FSTL1 may attenuate epithelial to mesenchymal transition in ccRCC. Microarray assay indicated that NF-B and HIF-2 pathways were activated following FSTL1 knockdown in ccRCC cells. Our study indicates that FSTL1 serves as a tumor suppressor in ccRCC, up-regulation of FSTL1 in cancer cells may be a candidate target therapy for advanced ccRCC.
Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma.
Specimen part, Cell line
View SamplesRNA localization is a fundamental mechanism for controlling the spatial regulation of protein synthesis within cells, as well as differential cell fates during early development. Localized RNAs are known to control critical aspects of early Xenopus development, but few have been studied in detail. We set out to identify novel transcripts localized to the vegetal cortex of Xenopus oocytes, one of the best-studied examples of RNA localization. We identified over 400 transcripts enriched in the vegetal cortex, compared with whole oocytes. Included were many novel genes, as well as known genes not thought to undergo RNA localization. These data suggest that the role of RNA localization in early development is extensive and will provide a resource for identifying candidate regulatory genes for early developmental processes.
Identification of germ plasm-associated transcripts by microarray analysis of Xenopus vegetal cortex RNA.
Specimen part, Treatment
View SamplesThe sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown.
Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.
Specimen part
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