Transcriptomics

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Calcineurin/NFAT signaling inhibits myeloid hematopoiesis in mice.


ABSTRACT: 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

ORGANISM(S): Mus musculus  

SUBMITTER: Jan Fric   Benjamin Hofmann  Siti A Isa  jinmiao chen  Alessandra Mortellaro  Clarice Lim  Jinmiao Chen  Esther Koh  Paola Ricciardi-Castagnoli  Christiane Ruedl 

PROVIDER: E-GEOD-29094 | ArrayExpress | 2011-09-30

SECONDARY ACCESSION(S): GSE29094PRJNA140321

REPOSITORIES: GEO, ArrayExpress

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