Mus musculus
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ABSTRACT:
PROVIDER: PRJNA140321 | ENA |
REPOSITORIES: ENA
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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: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.
2011-10-01 | GSE29094 | GEO
Project description:Calcineurin/NFAT signaling pathway has been shown to play important roles in various tissues such as the immune system, cardiac muscle and neuron. Although recent studies have shown that the pathway is involved in the regulation of hair growth, the precise mechanism is still unclear. In this study, we examine the molecular mechanism which is regulated by calcineurin/NFAT pathway, using two specific inhibitors for the pathway. Transcriptional profiling of human keratinocyte cell line, PHK cells, comparing control untreated PHK cells with cyclosporin A (CsA)-treated or 11R-VIVIT-treated PHK cells. Goal was to identify the effects of NFAT inhibitors on PHK cell proliferation. Cyclosporine A is a chemical compound, which strongly inhibits calcineurin phosphatase activity cooperating with cyclophilin, resulting in inhibition of NFAT signaling pathway. 11R-VIVIT is a cell-permeable peptide, which specifically interacts with NFAT and inhibits its binding to calcineurin, resulting in competitive inhibition of NFAT signaling pathway. Three-condition experiment; untreated PHK cells, CsA-treated PHK cells and 11R-VIVIT-treated PHK cells. Supplementary files: Significantly up-regulated genes across 4 different comparisons.
2010-11-08 | E-GEOD-25175 | biostudies-arrayexpress
Project description:Complex regulatory mechanisms control continuous maintenance of myeloid progenitors and renewal of differentiated cells. Transcription factors play a important role in these processes. Here we report that the activation the calcineurin-NFAT signaling pathway inhibit the proliferation of myeloid granulocyte-monocyte progenitor (GMP). Myeloid progenitor subtypes possessed different susceptibilities to Ca2+ flux induction and consequently differential engagement of the calcineurin-NFAT pathway. This study show that inhibition of the calcineurin-NFAT pathway enhanced proliferation of GMPs both in vivo and in vitro. The calcineurin-NFAT signaling in GMPs is initiated through Flt3-L. The inhibition of the calcineurin-NFAT pathway altered the expression of the cell cycle regulation genes CDK4, CDK6, and CDKN1A, thus enabling faster cell cycle progression. The extensive use of NFAT inhibitors in the clinic should take into account that, in addition to the immunosuppression role in lymphoid cells, these NFAT inhibitors also affect the maintenance of the myeloid compartment. Microarray technology was used to understand the effects of NFAT inhibitors on C-kit enriched lineage negative cells.
2014-12-31 | GSE47208 | GEO
Project description:Calcineurin/NFAT signaling pathway has been shown to play important roles in various tissues such as the immune system, cardiac muscle and neuron. Although recent studies have shown that the pathway is involved in the regulation of hair growth, the precise mechanism is still unclear. In this study, we examine the molecular mechanism which is regulated by calcineurin/NFAT pathway, using two specific inhibitors for the pathway. Transcriptional profiling of human keratinocyte cell line, PHK cells, comparing control untreated PHK cells with cyclosporin A (CsA)-treated or 11R-VIVIT-treated PHK cells. Goal was to identify the effects of NFAT inhibitors on PHK cell proliferation. Cyclosporine A is a chemical compound, which strongly inhibits calcineurin phosphatase activity cooperating with cyclophilin, resulting in inhibition of NFAT signaling pathway. 11R-VIVIT is a cell-permeable peptide, which specifically interacts with NFAT and inhibits its binding to calcineurin, resulting in competitive inhibition of NFAT signaling pathway.
2010-11-08 | GSE25175 | GEO
Project description:Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-NFAT pathway, such as Cyclosporine A or Tacrolimus, are commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threating conditions. A component of the A. fumigatus cell wall, β-glucan, is recognized by dendritic cells via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important anti-fungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.
2016-12-31 | GSE71936 | GEO
Project description:Inhibition of calcineurin-NFAT pathway at the early stage can block somatic cell reprogramming. In order to study how the calcineurin-NFAT pathway contributes to the early stage of reprogramming, we designed this microarray experiment and tried to find out which genes or signalings were changed after inhibition of calcineurin-NFAT signaling by CSA (a specific inhibitor of calcineurin-NFAT pathway).
2015-12-01 | GSE67739 | GEO
Project description:Genome-wide analysis of gene expression regulated by calcineurin-NFAT signaling in mouse embryonic stem cells
| PRJNA126093 | ENA
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
Project description:Granulocyte-monocyte progenitor cell cycle regulation occurs through calcium flux and calcineurin-NFAT signaling via Flt3-L
| PRJNA205108 | ENA