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Publication : Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages.

First Author  Wilcox NS Year  2023
Journal  iScience Volume  26
Issue  12 Pages  107985
PubMed ID  38047075 Mgi Jnum  J:360276
Mgi Id  MGI:7797624 Doi  10.1016/j.isci.2023.107985
Citation  Wilcox NS, et al. (2023) Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages. iScience 26(12):107985
abstractText  Tissue resident macrophages are largely of embryonic (fetal liver) origin and long-lived, while bone marrow-derived macrophages (BMDM) are recruited following an acute perturbation, such as hypoxia in the setting of myocardial ischemia. Prior transcriptome analyses identified BMDM and fetal liver-derived macrophage (FLDM) differences at the RNA expression level. Posttranscriptional regulation determining mRNA stability and translation rate may override transcriptional signals in response to hypoxia. We profiled differentially regulated BMDM and FLDM transcripts in response to hypoxia at the level of mRNA translation. Using a translating ribosome affinity purification (TRAP) assay and RNA-seq, we identified non-overlapping transcripts with increased translation rate in BMDM (Ly6e, vimentin, PF4) and FLDM (Ccl7, Ccl2) after hypoxia. We further identified hypoxia-induced transcripts within these subsets that are regulated by the RNA-binding protein HuR. These findings define translational differences in macrophage subset gene expression programs, highlighting potential therapeutic targets in ischemic myocardium.
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