Calcineurin signaling regulates neural induction through antagonizing the BMP pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54217 | GEO | 2014/04/01
SECONDARY ACCESSION(S): PRJNA235950
REPOSITORIES: GEO
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Project description:Calcineurin activity is required for neural differentiation of embryonic stem cells (ESC). We assessed gene expression changes at several time points of in vitro ESC to neural differentiation when calcineurin activity is inhibitied by its antagonist FK506 and Cyclosporin(CsA). d4, d6, d8, and d12 EBs of FK506/CsA treatment group (d3-8) and its non-treated control group were harvested from three independent experiments of in vitro differentiation of 46C mouse ESCs. Total RNA of each sample was extracted, reverse transcribed, labeled and hybridized to Affymetric Mouse Gene ST 1.0 Arrays.
2014-04-01 | E-GEOD-54217 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
2019-11-23 | GSE140882 | GEO
Project description:The calcineurin inhibitor immunosuppressant cyclosporin A (CsA) soon gained clinical application, and became a standard of care in organ transplantation, as well as an important treatment option in a variety of autoimmune diseases. The immunosuppressive effect of CsA is mainly attributed to inhibiting calcineurin phosphatase activity, consequently favouring the inactive phosphorylated form of nuclear factor of activated T cells (NFAT). Renal toxicity is a serious adverse effect of CsA, but the underlying mechanisms are insufficiently understood. CsA has also been shown to induce episodic hypoxia (Fähling et al, 2017; doi: 10.1111/apha.12811). Here, we sought to identify molecular mechanisms of CsA nephrotoxicity.
2021-02-22 | GSE111516 | GEO
Project description:In order to identify calcineurin pathway-regulated genes, we compared the genome-wide expression profile of wild-type with FK506-treated wild-type, cna1, and crz1 mutants. We expect that FK506-treated wild-type will have similar expression profile with that of the cna1 mutant. In response to calcineurin inhibitor FK506, the up- and down-regulated by FK506 were 113 and 87 genes, respectively (cutoff q < 0.001). The genes regulated by FK506 are largely overlapped (90%, 180/200) with those of cna1 mutant. Interestingly, FK506 induced 20 distinct genes other than that of the cna1 mutant. These genes encode proteins involved in plasma membrane ATP-bindding cassette (ABC) multidrug transporters (PDR15, PDR5, and YOR1), amino acid transporters (ALP1 and YBT1), and transcription factors (CUP2 and INO2). We also identified 34 genes regulated by calcineurin and Crz1. These genes encode proteins involved in cell wall biosynthesis (YPS5, YPS1, YSR3, YPC1, PIR1, HOR7, and NTE1), heat shock protein responses (SBA1 and GRE2), regulator of calcineurin (RCN2), and other functions.
2011-09-01 | GSE31167 | GEO
Project description:In order to identify calcineurin pathway-regulated genes, we compared the genome-wide expression profile of wild-type with FK506-treated wild-type, cna1, and crz1 mutants. We expect that FK506-treated wild-type will have similar expression profile with that of the cna1 mutant. In response to calcineurin inhibitor FK506, the up- and down-regulated by FK506 were 113 and 87 genes, respectively (cutoff q < 0.001). The genes regulated by FK506 are largely overlapped (90%, 180/200) with those of cna1 mutant. Interestingly, FK506 induced 20 distinct genes other than that of the cna1 mutant. These genes encode proteins involved in plasma membrane ATP-bindding cassette (ABC) multidrug transporters (PDR15, PDR5, and YOR1), amino acid transporters (ALP1 and YBT1), and transcription factors (CUP2 and INO2). We also identified 34 genes regulated by calcineurin and Crz1. These genes encode proteins involved in cell wall biosynthesis (YPS5, YPS1, YSR3, YPC1, PIR1, HOR7, and NTE1), heat shock protein responses (SBA1 and GRE2), regulator of calcineurin (RCN2), and other functions. 5 sample wheel hybridization design with dye swaps totaling 10 arrays replicated 2 times to include an additional set of biological replicates. 20 arrays total.
2011-08-31 | E-GEOD-31167 | biostudies-arrayexpress
Project description:Self-renewal and pluripotency are hallmarks of embryonic stem cells (ESCs). However, signaling pathways triggering their transition from self-renewal to differentiation are not well defined. Here, we report that the calcineurin-NFAT signaling pathway is both necessary and sufficient to switch ESCs from an undifferentiated state to early differentiation.To gain an insight into the function of calcinerin-NFAT signaling in ESC lineage commitment, we examined the repertoire of genes changed after LIF withdrawal alone, LIF withdrawal in the presence of cyclosporine A (CsA), a specific inhibitor of calcinerin and forced expression of active forms of calcineurin (deltaCnA) in the presence of LIF,and identified distinct classes of up and down regulated genes by calcineurin-NFAT signaling in mouse embryonic stem cells. Total RNA obtained from CGR8 ES cells under the following conditions: withdrawal of LIF for 0, 1 and 3 days; withdrawal of LIF for 0, 1 and 3 days in the presence of CsA, and induced expression of deltaCnA by withdrawal of Tc for 0, 1 and 4 days in ideltaCnAES cells.Hybridized to Illumina Sentrix Mouse-6 v1.1 Beadhips
2011-01-01 | E-GEOD-21378 | biostudies-arrayexpress
Project description:Nuclear factor of activated T cells (NFAT) comprises a family of transcription factors that regulate T cell development, activation and differentiation. NFAT signaling can also mediate granulocyte and DC activation, but it is unknown whether NFAT influences their development from progenitors. Here we report a novel role for calcineurin/NFAT signaling as a negative regulator of myeloid hematopoiesis. Reconstituting lethally-irradiated mice with hematopoietic stem cells expressing an NFAT-inhibitory peptide resulted in enhanced development of the myeloid compartment. Culturing bone marrow cells with Flt3-L and Cyclosporin A, which inhibits NFAT signaling, increased numbers of differentiated DC. Global gene expression analysis of untreated DC and NFAT-inhibited DC revealed differential expression of transcripts that regulate cell cycle and apoptosis. Thus, calcineurin/NFAT signaling negatively regulates myeloid lineage development. The finding that NFAT acts as a negative regulator of myeloid development provides novel insight in understanding immune responses during treatment with calcineurin/NFAT inhibitors as Cyclosporin A. bone marrow cells from C57B/6 mice were stimulated in Flt3-L suplemented media in presence or absence of calcineurin/NFAT inhibitor Cyclosporin A, samples in 3 biological replicates
2011-09-30 | E-GEOD-29094 | biostudies-arrayexpress
Project description:Gene expression was quantified in crz1 delete S. cerevisae cells over a time course following calcineurin activation by CaCl2. Cells were pretreated with buffer or the calcineurin inhibitor FK506 to allow the identification of calcineurin-regulated genes. A strain with a calcineurin-resistant mutation in the transcription factor Hcm1 was also examined. We show that calcineurin activation leads to downregulation of a many clusters of cell cycle-regulated genes, including those expressed at the G1/S and G2/M transitions.
2020-01-14 | GSE115013 | GEO
Project description:Gene expression was quantified in crz1 hog1 delete S. cerevisae cells over a time course following calcineurin activation by CaCl2. Cells were pretreated with buffer or the calcineurin inhibitor FK506 to allow the identification of calcineurin-regulated genes. We show that calcineurin-dependent downregulation of G1/S genes is partly dependent on the osmostress-activated kinase Hog1.
2020-01-14 | GSE115014 | GEO
Project description:Self-renewal and pluripotency are hallmarks of embryonic stem cells (ESCs). However, signaling pathways triggering their transition from self-renewal to differentiation are not well defined. Here, we report that the calcineurin-NFAT signaling pathway is both necessary and sufficient to switch ESCs from an undifferentiated state to early differentiation.To gain an insight into the function of calcinerin-NFAT signaling in ESC lineage commitment, we examined the repertoire of genes changed after LIF withdrawal alone, LIF withdrawal in the presence of cyclosporine A (CsA), a specific inhibitor of calcinerin and forced expression of active forms of calcineurin (deltaCnA) in the presence of LIF,and identified distinct classes of up and down regulated genes by calcineurin-NFAT signaling in mouse embryonic stem cells.
2011-01-01 | GSE21378 | GEO