Abstract 16736: The Long Intergenic Non-coding RNA Landscape in Human Macrophage Activation
Introduction: With remarkable plasticity and wide-ranging states of activation in response to environmental challenges, macrophages play a central role in pathogenesis of cardiometabolic diseases (CMDs). However, the long non-coding RNA landscape that regulates macrophage activation is poorly defined.
Hypothesis: Comprehensive analysis of long intergenic non-coding RNA (lincRNA) expression profiles reveals novel macrophage lincRNA signature.
Methods: We used deep RNA sequencing to assemble the lincRNA transcriptome in human macrophages (HMDM, N=6 subjects) at rest and also after stimulation with lipopolysaccharide and interferon-gamma for M1-like inflammatory activation, and interleukin-4 for M2-like anti-inflammatory activation (A).
Results: Through de novo assembly, we identified 2,766 macrophage lincRNAs including 861 previously unannotated novel lincRNAs. The majority (86%) was non-syntenic, or syntenic but not annotated in mouse genomes (B). Many macrophage lincRNAs also demonstrated tissue-enriched transcription patterns (12 %) and enhancer-like chromatin signatures (62 %). Macrophage activation, particularly to the M1 phenotype, markedly altered the lincRNA expression profiles with 96 lincRNAs differentially expressed (fold-change > 2 and FDR < 0.01) (C), suggesting a role for lincRNAs in macrophage inflammatory response. A subset of CMD trait-associated variants in genome-wide association studies tagged lincRNAs that may contribute to macrophage-related human diseases. Induced pluripotent stem cell-derived macrophages (IPSDM) recapitulated lincRNA transcriptome of primary macrophage and provide a high-fidelity model system to study function of lincRNAs in human macrophage biology (D).
Conclusion: In summary, high-resolution transcriptomics identified 100s of lincRNAs that form part of the cellular response in macrophage activation as well as specific macrophage lincRNAs associated with human CMDs.
Author Disclosures: H. Zhang: None. C. Xue: None. Y. Wang: None. W. Li: None. S. Nunez: None. A.S. Foulkes: None. J.J. Lin: None. C.C. Hinkle: None. W. Yang: None. E.E. Morrisey: None. D.J. Rader: None. M. Li: None. M.P. Reilly: None.
- © 2016 by American Heart Association, Inc.