The lncRNA landscape of cardiac resident macrophages and identification ofSchlafenlncas a regulator of macrophage migratory function

Author:

Dueck AnneORCID,Althaus Lara,Heise Kathrin,Esfandyari Dena,Baygün Seren,Brandes Ralf P.,Gagneur JulienORCID,Jaé Nicolas,Knolle Percy,Leisegang Matthias S.,Maegdefessel Lars,Meitinger ThomasORCID,Petzold Niklas,Ramanujam Deepak,Sager Hendrik,Schulz Christian,Theodorakis Evangelos,Uzonyi Anna,Weinberger Tobias,Bader Michael,Schmidt-Supprian Marc,Engelhardt Stefan

Abstract

ABSTRACTCardiac resident macrophages (crMPs) were recently shown to exert pivotal functions in cardiac homeostasis and disease, but the underlying molecular mechanisms are largely unclear. Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulatory molecules in a number of cell types, but neither the identity nor the molecular mechanisms of lncRNAs in crMPs are known. Here, we have employed deep RNA-seq and single cell RNA sequencing to resolve the crMP lncRNA landscape from healthy and diseased murine myocardium. CrMPs express previously unknown and highly cell type-specific lncRNAs, among which one lncRNA, termedSchlafenlnc, was particularly abundant and enriched in crMPs. We foundSchlafenlncto be necessary for migration-associated gene expression in macrophagesin vitroandin vivoand essential for their adhesion and migration. Collectively, our data provide a basis to the systematic characterization of lncRNAs in crMPs and establishSchlafenlncas a critical regulator of macrophage migratory functions.

Publisher

Cold Spring Harbor Laboratory

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