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

Project Information

GLIA-LNC

Grant agreement ID: 101032677

DOI

10.3030/101032677

Project closed

EC signature date 16 April 2021

Start date 1 February 2022

End date 28 February 2024

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 162 806,40

EU contribution

€ 162 806,40

Coordinated by

TECHNISCHE UNIVERSITAET MUENCHEN
Germany

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

Reporting period: 2022-02-01 to 2024-01-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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