All living cells rely on the communication with other cells to ensure their function and survival. Molecular signals are sent among cells of the same cell type and from cells of one cell type to another. In cancer, not only the cancer cells themselves are responsible for the malignancy, but also stromal (non-cancerous) cells and the molecular signals they send to cancer cells are important factors that determine the severity and outcome of the disease. Therefore, the identification of stromal signals and their influence on cancer cells is important when looking for novel treatment strategies.
Causal Modeling of Cancer-Stromal Communication Identifies PAPPA as a Novel Stroma-Secreted Factor Activating NFκB Signaling in Hepatocellular Carcinoma.
Specimen part
View SamplesMaintenance of CG methylation (mCG) patterns is essential for chromatin-mediated epigenetic regulation of transcription in plants and mammals. Using successive generations of an Arabidopsis thaliana mutant deficient in maintaining mCG, we found that mCG loss triggered genome-wide activation of alternative epigenetic mechanisms. However, these mechanisms involving RNA-directed DNA methylation, inhibiting expression of DNA demethylases, and retargeting of histone H3K9 methylation act in a stochastic and uncoordinated fashion. As a result, new and aberrant epigenetic patterns were progressively formed over several plant generations in the absence of mCG. Interestingly, the unconventional redistribution of epigenetic marks was necessary to rescue the loss of mCG, since mutant plants impaired in rescue activities were severely dwarfed and sterile. Our results provide evidence that mCG is a central coordinator of epigenetic memory that secures stable transgenerational inheritance in plants.
Transgenerational stability of the Arabidopsis epigenome is coordinated by CG methylation.
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View SamplesOne of the most common genetic alterations in acute myeloid leukemia is the internal tandem duplication (ITD) in the FLT3 receptor for cytokine FLT3 ligand (FLT3L). The constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on normal hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. We report that young pre-leukemic mice with the Flt3ITD knock-in allele manifest an expansion of all DCs including classical (cDCs) and plasmacytoid (pDCs). The expansion originated in DC progenitors, occurred in a cell-intrinsic manner and was further enhanced in Flt3ITD/ITD mice. The mutation caused the downregulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T cells (Tregs). Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity in the absence of Tregs. Thus, the FLT3-ITD mutation directly affects DC development, thereby indirectly modulating T cell homeostasis and supporting Treg expansion. This effect of FLT3-ITD may subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. Overall design: Sorted splenic dendritic cell subsets from either Flt3+/+ or Flt3ITD/+ mice were sequenced for mRNA profiling. For each subset per genotype contains 2-3 replicates, all from independent experiments.
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.
Specimen part, Cell line, Subject
View SamplesAddition of 3 new arrays made from carbon limited chemostat of CENPK113-7D and 3 new arrays made from aerobic carbon limited chemostat of CENPK113-7D Complmentary data to the data of the serie GSE1723.
Exploiting combinatorial cultivation conditions to infer transcriptional regulation.
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View SamplesRaw expression values (CHP data) for transcriptional profiling of the response of Saccharomyces cerevisiae to challenges with various weak organic acids
Generic and specific transcriptional responses to different weak organic acids in anaerobic chemostat cultures of Saccharomyces cerevisiae.
No sample metadata fields
View SamplesInterleukin-1 receptor associated kinase 1 (IRAK1) is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation. Here, we show that IRAK1 promotes Th17 development by mediating IL-1 induced upregulation of IL-23R and subsequent STAT3 phosphorylation, thus enabling sustained IL-17 production. Moreover, we show that IRAK1 signaling fosters Th1 differentiation by mediating T-bet induction and counteracts Treg generation. Cotransfer experiments revealed that Irak1-deficient CD4+ T cells have a cell-intrinsic defect in generating Th1 and Th17 cells under inflammatory conditions in spleen, mesenteric lymph nodes and colon tissue. Furthermore, IRAK1 expression in T cells was shown to be essential for T cell accumulation in the inflamed intestine and mLNs. Transcriptome analysis ex vivo revealed that IRAK1 promotes T cell activation and induction of gut-homing molecules in a cell-intrinsic manner. Accordingly, Irak1-deficient T cells failed to upregulate surface expression of 47 integrin after transfer into Rag1-/- mice and their ability to induce colitis was greatly impaired. Lack of IRAK1 in recipient mice provided additional protection from colitis. Therefore, IRAK1 plays an important role in intestinal inflammation by mediating T cell activation, differentiation and their accumulation in the gut. Thus, IRAK1 is a promising novel target for therapy of inflammatory bowel diseases.
IRAK1 Drives Intestinal Inflammation by Promoting the Generation of Effector Th Cells with Optimal Gut-Homing Capacity.
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View Samplesgene expression modification after miR-182 inhibition, day 2 and day 7 after ischemic reperfusion injury
miR-182-5p Inhibition Ameliorates Ischemic Acute Kidney Injury.
Specimen part
View SamplesBackground
Combinatorial effects of environmental parameters on transcriptional regulation in Saccharomyces cerevisiae: a quantitative analysis of a compendium of chemostat-based transcriptome data.
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View SamplesHuman aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the gold standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.
A mesenchymal stromal cell gene signature for donor age.
Sex, Age
View Samplesexpression profiles kPSCs versus cMSC
The human kidney capsule contains a functionally distinct mesenchymal stromal cell population.
Specimen part
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