Filters
Technology
Platform
GSE33672
Homo sapiens
4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hsa-mir-365-2 is one of the two precursors that give rise to miR-365. We discovered that miR-365 directly regulates a lung cancer and developmental gene termed thyroid transcription factor 1 (TTF-1 or NKX2-1).
Publication Title
MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Comparative analyses of Mex67 and Npl3 binding to mRNA at normal growth condition (25째C) and upon shift to heat stress (30 min, 42째C). Overall design: Examination of two biological RNA Co-IP replicates of Mex67, Npl3 and no tag control at 25째C and upon shift to 30 min at 42째C (Heat stress) and subsequent Illumina RNA deep-sequencing
Publication Title
mRNA quality control is bypassed for immediate export of stress-responsive transcripts.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- NextSeq 500
Description
During chronic viral infection, the inflammatory function of CD4 T cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this T cell adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T cells during chronic infection. Unexpectedly, our analyses revealed an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T cells or deletion of Il10 specifically in Tfh cells resulted in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling was required for sustaining germinal center reactions. Lastly, we demonstrate that IL-27 and type I IFNs differentially regulate the formation of this protective IL-10-producing Tfh subset. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection. Overall design: One sample prepared using 10x Genomics Chromium platform
Publication Title
Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Non-tumor-reactive T cells are characterized by the inabilitzy to lyse autologous tumor cells, low to intermediate avidity TCRs and lack of NY-ESO-1 peptide tetramer binding. However most strikingly, non-tumor-reactive T cells are characterized by a molecular program associated with division arrest anergy with elevated expression of the inhibitory molecule p27kip1. This is accompanied by elevated expression of inhibitory molecules and reduced levels of transcription factors involved in T cell activation. Frequency analysis of the inhibited T cell population using the established molecular fingerprint as a novel biomarker might be applied for cancer vaccine development and optimization.
Publication Title
Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Based on studies in knockout mice, several inhibitory factors such as TGF-beta, IL-10, or CTLA-4 have been implicated as gate keepers of adaptive immune responses. Lack of these inhibitory molecules leads to massive inflammatory responses mainly mediated by activated T cells. In humans, the integration of these inhibitory signals for keeping T cells at a resting state is less well understood. To elucidate this regulatory network we assessed early genome-wide transcriptional changes during serum deprivation in human mature CD4+ T cells. The most striking observation was a "TGF-beta loss signature" defined by downregulation of many known TGF-beta target genes. Moreover, numerous novel TGF-beta target genes were identified that are under the suppressive control of TGF-beta. Expression of these genes was upregulated once TGF-beta signaling was lost during serum deprivation and again suppressed upon TGF-beta reconstitution. Constitutive TGF-beta signaling was corroborated by demonstrating phosphorylated SMAD2/3 in resting human CD4+ T cells in situ, which were dephosphorylated during serum deprivation and re-phosphorylated by minute amounts of TGF-beta. Loss of TGF-beta signaling was particularly important for T cell proliferation induced by low-level T cell receptor and costimulatory signals. We suggest TGF-beta to be the most prominent factor actively keeping human CD4+ T cells at a resting state.
Publication Title
Human resting CD4+ T cells are constitutively inhibited by TGF beta under steady-state conditions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite the importance of inter-cellular communication networks in regulating stem cell fate decisions, very little is known about the topology, dynamics, or functional significance. Using human blood stem cell cultures as an experimental paradigm, we present a novel bioinformatic approach to integrate genome-scale molecular profiles (transcriptome and secretome) and publicly available databases to reconstruct soluble factor-mediated inter-cellular signalling networks regulating blood stem cell fate decisions.
Publication Title
Dynamic interaction networks in a hierarchically organized tissue.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Pluripotent stem cells (PSCs) exist in multiple stable states, each with specific cellular properties and molecular signatures. The process by which pluripotency is either maintained or destabilized to initiate specific developmental programs is poorly understood. We have developed a model to predict stabilized PSC gene regulatory network (GRN) states in response to combinations of input signals. While previous attempts to model PSC fate have been limited to static cell compositions, our approach enables simulations of dynamic heterogeneity by combining an Asynchronous Boolean Simulation (ABS) strategy with simulated single cell fate transitions using a Strongly Connected Components (SCCs). This computational framework was applied to a reverse-engineered and curated core GRN for mouse embryonic stem cells (mESCs) to simulate responses to LIF, Wnt/ß-catenin, FGF/ERK, BMP4, and Activin A/Nodal pathway activation. For these input signals, our simulations exhibit strong predictive power for gene expression patterns, cell population composition, and nodes controlling cell fate transitions. The model predictions extend into early PSC differentiation, demonstrating, for example, that a Cdx2-high/Oct4-low state can be efficiently generated from mESCs residing in a naïve and signal-receptive state sustained by combinations of signaling activators and inhibitors. Overall design: Examination of perturbed PSCs versus control PSCs and mesoderm progenitors Mouse pluripotent stem cells were grown on tissue culture plates for two days in serum-containing, feeder free medium supplemented with the following cytokines/small molecules: 2i = CHIR99021 (Reagents Direct 27-H76 – 3µM) & PD0325901 (Reagents Direct 39-C68 – 1µM) Jaki = JAK inhibitor (EMD Millipore 420097 – 2.0µM) BMP = BMP4 (R&D Systems 314-BP-010 – 10ng/ml) Alk5i = ALK5 inhibitor II (Cedarlane ALX-270-445 - 10µM)
Publication Title
Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate transitions.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 22 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Background: Development of target specific therapeutics greatly benefits from simultaneous identification of biomarkers to determine aspects of bioactivity, drug safety and efficacy or even treatment outcome. This is particularly important when targeting pleiotropic factors such as the TGFbeta system. TGFbeta has become a prime target for cancer therapeutics since inhibition of TGFbeta signaling simultaneously attacks the tumor and its microenvironment. Methods: Here we introduce blood transcriptomics followed by a defined set of validation assays as a promising approach to identify novel biomarkers for monitoring TGFbeta therapy. Findings: Our initial genome-wide analysis of transcription in peripheral blood revealed 12 candidate genes specifically regulated in peripheral blood by the TGFbeta receptor I kinase inhibitor LY2109761. In subsequent in vitro and in vivo molecular and immunological analyses, the combined monitoring of gene regulation of three genes, namely TMEPAI, OCIAD2, and SMAD7 was established as novel biomarkers for anti-TGFbeta based therapies. Interpretation: Overall, the proposed algorithm of biomarker identification is easily adapted towards other drug candidates for which gene regulation can be established in peripheral blood.
Publication Title
Application of T cell-based transcriptomics to identify three candidate biomarkers for monitoring anti-TGFbetaR therapy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The neural stem cell decision to self-renew or differentiate is tightly regulated by its microenvironment. Here, we have asked about this microenvironment, focusing on growth factors in the embryonic cortex at a time when it is largely comprised of neural precursor cells (NPCs) and newborn neurons. We show that cortical NPCs secrete factors that promote their maintenance while cortical neurons secrete factors that promote differentiation. To define factors important for these activities, we used transcriptome profiling to identify ligands produced by NPCs and neurons, cell surface mass spectrometry to identify receptors on these cells, and computational modeling to integrate these data. The resultant model predicts a complex growth factor environment with multiple autocrine and paracrine interactions. We tested this communication model, focusing on neurogenesis, and identified IFN, Nrtn and glial-derived neurotrophic factor (GDNF) as ligands with unexpected roles in promoting neurogenic differentiation of NPCs in vivo.
Publication Title
Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Samples of adherent and suspension cells undergoing reprogramming were collected at day 0, day2, day6, day15 (with doxycycline) and day25 (without doxycycline).
Publication Title
Derivation, expansion and differentiation of induced pluripotent stem cells in continuous suspension cultures.
Sample Metadata Fields
Specimen part
View Samples