Long non-coding RNAs that regulate glial cell function in the diseased heart

Informations projet

GLIA-LNC

N° de convention de subvention: 101032677

DOI

10.3030/101032677

Projet clôturé

Date de signature de la CE 16 Avril 2021

Date de début 1 Février 2022

Date de fin 28 Février 2024

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 162 806,40

Contribution de l’UE

€ 162 806,40

Coordonné par

TECHNISCHE UNIVERSITAET MUENCHEN
Germany

Periodic Reporting for period 1 - GLIA-LNC (Long non-coding RNAs that regulate glial cell function in the diseased heart)

Période du rapport: 2022-02-01 au 2024-01-31

Résumé du contexte et des objectifs généraux du projet

Despite progress in acute treatment, heart disease remains the leading cause of death worldwide. Current treatments fail to prevent cellular disease processes or to promote tissue recovery after cardiac events. Since heart disease is accompanied by dramatic changes in neuronal integrity, understanding of the factors that regulate cardiac neuronal function and remodelling could facilitate development of novel therapies for heart disease.
Glial cells (GCs) cover almost all neuronal cell surfaces and regulate neuronal function and remodelling. While neuronal function and remodelling play a key role in heart disease, little is known about the role of cardiac GCs.
During the GLIA-LNC project we characterized the changes in cardiac GCs during pathological cardiovascular remodelling which allowed us to identify several long non-coding RNAs (lncRNAs) that determine cardiac GC functions involved in neuronal remodelling. Since lncRNAs represent attractive therapeutic targets, follow up experiments will determine if therapeutic targeting of the identified GC lncRNAs could rescue neuronal integrity during heart disease.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

We optimized and implemented methods to characterize the cardiac glial cells at single cell resolution using a combination of single cell transcriptomics and 3D imaging of intact, optically cleared hearts.
The state-of-the-art imaging methods enabled us to examine the distribution of glial cells across the heart and their changes during heart diseased induced remodelling of cardiac innervation.
Single cell transcriptomics enables us to detect different types of GCs and their changes during cardiac disease. We subsequently used this data to identify cardiac GC lncRNAs that are conserved and deregulated during disease and expected to be functionally relevant.
Finally, we validated the functional importance of two of these lncRNA candidates by knocking them down in a complex ex vivo assay for nerve sprouting after injury.
These findings have been disseminated in a small circle to safeguard the option for patenting and will be submitted for publication when follow-up experiments are completed.
The knowledge and expertise obtained during this project has been actively shared through seminars and workshops, as well as supervision, teaching, and outreach activities.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Despite the established importance of cardiac innervation on heart function, little is known about the role of GCs function in heart disease and the role of ncRNAs in GCs is entirely unknown.
The GLIA-LNC project has enabled us to adopt and implement state-of-the-art technologies including single cell transcriptomics and wholemount 3D imaging to provide novel insights into cardiac GCs and their lncRNAs during heart disease. Moreover, we have identified evolutionarily conserved lncRNAs that appear to regulate glial cell function during ex vivo neuronal remodelling and might provide new therapeutic targets for heart disease.

Glial cells of a ganglion explant