Transcriptional profiling of eosinophil subsets in Interleukin-5 transgenic mice
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ABSTRACT:
PROVIDER: PRJNA438949 | ENA |
REPOSITORIES: ENA
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Project description:Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. Interleukin-5 (IL-5) is a critical regulator of eosinophil development, controlling proliferation, differentiation and maturation of the lineage. Mice that constitutively express IL-5 have more than 10 fold more eosinophils in the haematopoietic organs than their wild type counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in wild type mice. In this study we assessed transcription in myeloid progenitors, eosinophil precursors and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilised these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend towards quiescence along the trajectory. Additionally we found gene expression changes associated with constitutive IL-5 signalling in eosinophil progenitors, many of which were not observed in eosinophils.
2018-03-20 | GSE112010 | GEO
Project description:Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL-5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL-5 have in excess of 10-fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in WT mice. In this study, we assessed transcription in myeloid progenitors, eosinophil precursors, and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilized these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend toward quiescence along the trajectory. Additionally, we found gene expression changes associated with constitutive IL-5 signaling in eosinophil progenitors, many of which were not observed in eosinophils.
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Project description:To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including eosinophil-lineage commitment (eosinophil progenitor [EoP] compared to granulocyte-monocyte progenitor [GMP]) and lineage maturation (eosinophil compared to EoP). Our analyses revealed markedly greater transcriptome alterations associated with eosinophil maturation (1199 genes) compared to eosinophil-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Our analyses also delineated a 976 gene eosinophil-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with eosinophils. Epigenomic studies revealed that genes that were specifically induced with eosinophil-lineage commitment in EoPs were “poised” with active chromatin marks in GMPs, despite not being expressed in GMPs. In contrast, a majority of the genes that were highly and specifically induced with maturation in eosinophils was not associated with poised chromatin, suggesting distinct epigenetic regulation between genes induced with lineage commitment compared to genes induced with cell maturation during eosinophil development.
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Project description:The goal of this study is to evaluate the function of eosinophil-derived neurotoxin (EDN) in eosinophilic chronic rhinosinusitis (ECRS) pathogenesis and assess its potential as a disease activity marker.
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