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

Dueck, A.; Althaus, L.; Heise, K.; Esfandyari, D.; Bayguen, S.; Brandes, R. P.; Gagneur, J.; Jae, N.; Knolle, P.; Leisegang, M. S.; Maegdefessel, L.; Meitinger, T.; Petzold, N.; Ramanujam, D.; Sager, H.; Schulz, C.; Theodorakis, E.; Uzonyi, A.; Weinberger, T.; Bader, M.; Schmidt-Supprian, M.; Engelhardt, S.

2022-12-01 cell biology
10.1101/2022.11.30.518576 bioRxiv
Show abstract

Cardiac 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, termed Schlafenlnc, was particularly abundant and enriched in crMPs. We found Schlafenlnc to be necessary for migration-associated gene expression in macrophages in vitro and in vivo and essential for their adhesion and migration. Collectively, our data provide a basis to the systematic characterization of lncRNAs in crMPs and establish Schlafenlnc as a critical regulator of macrophage migratory functions.

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