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

Nicholas S Wilcox; Timur O Yarovinsky; Prakruti Pandya; Vinod S Ramgolam; Albertomaria Moro; Yinyu Wu; Stefania Nicoli; Karen K Hirschi; Jeffrey R Bender

doi:10.1016/j.isci.2023.107985

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

iScience. 2023 Sep 21;26(12):107985. doi: 10.1016/j.isci.2023.107985. eCollection 2023 Dec 15.

Authors

Nicholas S Wilcox^{1

2}, Timur O Yarovinsky^{1

2}, Prakruti Pandya^{1

2}, Vinod S Ramgolam^{1

2}, Albertomaria Moro^{1

3}, Yinyu Wu^{1

3}, Stefania Nicoli^{1

3}, Karen K Hirschi^{1

3}, Jeffrey R Bender^{1

2}

Affiliations

¹ Department of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT USA.
² Department of Immunobiology, and Yale University School of Medicine, New Haven, CT 06511, USA.
³ Department of Genetics, Yale University School of Medicine, New Haven, CT 06511, USA.

Abstract

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.

Keywords: Biological sciences; Cell biology; Immunology; Molecular biology.

Abstract

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