Calcineurin/NFAT signalling inhibits myeloid haematopoiesis.
Bottom Line: Reconstituting lethally irradiated mice with haematopoietic stem cells expressing an NFAT-inhibitory peptide resulted in enhanced development of the myeloid compartment.Global gene expression analysis of untreated DC and NFAT-inhibited DC revealed differential expression of transcripts that regulate cell cycle and apoptosis.In conclusion, these results provide evidence that calcineurin/NFAT signalling negatively regulates myeloid lineage development.
Affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.Show MeSH
Related in: MedlinePlus
Mentions: In further studies, these data were confirmed using freshly transduced primary BM cells to replicate the results obtained with HSC lines. Freshly isolated BM cells were transduced with either VIVIT-eGFP or control tdTomato constructs before the cells were sorted and then injected into irradiated hosts in the ratio 30% VIVIT-eGFP competitors to 70% control tdTomato cells. Under these conditions using primary cells and excluding any possible interference of NUP-HOXB4 constructs, we still observed a preferential expansion of calcineurin/NFAT-impaired myeloid cells over controls. The ratio of granulocytes, DC and T cells was analysed at weeks 4–8 and 12 weeks post-engraftment. The competitive advantage of VIVIT-expressing myeloid cells over the mock-transduced controls was still evident (Fig 3).
Affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.