Long non-coding RNA in cardiac macrophages

The field of long non-coding RNAs (lncRNAs) has been rapidly growing within the last few years. As a class of molecules, they are until now only characterized by their length (> 200 nucleotides) and an apparent lack of coding potential. Based on data sets from high-throughput sequencing, several thousand genes have been identified to harbor potential lncRNAs (Mattick et al., Nat. Rev. Mol. Cell Biol., 2023). Although only very few have thus far been functionally characterized in the heart, these studies already indicate a fundamental impact of lncRNAs on cardiac development, function, and disease.

We are especially interested in the heart’s immune cells as they serve important functions in homeostasis and disease. We apply deep RNA-seq, single cell sequencing and CRIPSR-Cas technology, as well as cell-based assays, to study the impact of individual lncRNAs in vitro and in vivo. We have resolved the unique lncRNA repertoire of cardiac macrophages, and selected a subset for further characterization. One of these candidates, termed Schlafenlnc, is particularly abundant and enriched in this cardiac macrophages and , regulates the chemotaxis of these cells (Dueck et al., 2022). Currently, we test whether manipulation of this lncRNA or its molecular targets will promise as a new approach for the antiinflammatory treatment of human heart failure.

References:

1. Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen L, Chen R, Dean C, Dinger ME, Fitzgerald KA. Long non-coding RNAs : definitions , functions , challenges and recommendations. doi:10.1038/s41580-022-00566-8(link is external)

2. Dueck A, Althaus L, Heise K, Esfandyari D, Baygün S, Brandes RP, Gagneur J, Jaé N, Knolle P, Leisegang MS, 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. The lncRNA landscape of cardiac resident macrophages and identification of Schlafenlnc as a regulator of macrophage migratory function. bioRxiv 2022.11.30.518576; doi: 10.1101/2022.11.30.518576(link is external)