Hematopoietic overexpression of FOG1 does not affect B-cells but reduces the number of circulating eosinophils.
Camille Du Roure,Aude Versavel,Thierry Doll,Chun Cao,Vincent Pillonel,Gabriele Matthias,Markus Kaller,Jean-François Spetz,Patrick Kopp,Hubertus Kohler,Matthias Müller,Patrick Matthias +11 more
TL;DR: It is found that enforced expression of FOG-1 throughout all hematopoietic lineages led to a reduction in the number of circulating eosinophils, confirming and extending to mammals the known function of Fog-1 in this lineage.
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Abstract: We have identified expression of the gene encoding the transcriptional coactivator FOG-1 (Friend of GATA-1; Zfpm1, Zinc finger protein multitype 1) in B lymphocytes. We found that FOG-1 expression is directly or indirectly dependent on the B cell-specific coactivator OBF-1 and that it is modulated during B cell development: expression is observed in early but not in late stages of B cell development. To directly test in vivo the role of FOG-1 in B lymphocytes, we developed a novel embryonic stem cell recombination system. For this, we combined homologous recombination with the FLP recombinase activity to rapidly generate embryonic stem cell lines carrying a Cre-inducible transgene at the Rosa26 locus. Using this system, we successfully generated transgenic mice where FOG-1 is conditionally overexpressed in mature B-cells or in the entire hematopoietic system. While overexpression of FOG-1 in B cells did not significantly affect B cell development or function, we found that enforced expression of FOG-1 throughout all hematopoietic lineages led to a reduction in the number of circulating eosinophils, confirming and extending to mammals the known function of FOG-1 in this lineage.
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Eosinophil Development, Disease Involvement, and Therapeutic Suppression.
TL;DR: Human eosinophils have characteristic morphologic features, including a bilobed nucleus and cytoplasmic granules filled with cytotoxic and immunoregulatory proteins that are packaged in a specific manner, and the cytokine IL-5 specifically enhances eosInophil production and, along with other mediators, promotes eos inophil activation.
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Transcription Factors in Eosinophil Development and As Therapeutic Targets
TL;DR: A model is described wherein distinct classes of TFs work together via collaborative and hierarchical interactions to direct eosinophil development, and the therapeutic potential for targeting TFs to regulate eos inophil production is discussed.
IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data
TL;DR: IQCELL as discussed by the authors is a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data, which allows simulation of fundamental hypotheses governing developmental programs and help accelerate the design of strategies to control stem cell fate.
Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
TL;DR: In this article, a review of the role of EoP in asthma and discusses findings from clinical trials with various therapeutic targets is presented. But, they do not show that targeting single mediators downstream of the inflammatory cascade may not fully attenuate tissue eosinophilia due to the multiplicity of factors that can promote tissue eoophilia.
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Eosinophils: Old Players in a New Game.
TL;DR: A global, updated vision of the biology of eosinophils and the role of eanophils in respiratory diseases, particularly asthma is provided and new therapeutic strategies based on biological products in which eos inophil and their receptors are the main targets are summarized.
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