TELOCYTE IDENTITY – A DISTINCT CELL OR A DIFFERENT PHENOTYPE?
Project funded by UEFISCDI Ctr. no. 43/2021 (2021-2023)
Project code: PN-III-P4-ID-PCE-2020-2300
Coordinator: Victor Babeș National Institute of Pathology (IVB), Dr. Mihaela Gherghiceanu
Team: Daciana Marta, Laura Ceafalan, Leona Chițoiu, Tudor Emanuel Fertig, Victor Peteu, George Terinte-Balcan, Gabriela Vîlciu, Petruța Mușat
The strategies to stimulate endogenous cardiomyocyte renewal depend on our understanding of molecular and cellular mechanisms involved, in situ. To contribute to this effort, this study aims to investigate the identity of telocytes (TCs) as a type of cardiac interstitial cell.
Although the role of the mesenchymal compartment in tissue homeostasis or disease is increasingly recognized, the relative contribution of distinct cell subsets to these processes remains poorly understood. The main limitation has been the lack of specific markers able to discriminate between the different interstitial cells. Despite the importance of this field, there have been limited efforts to systematically recognize the identity of cells involved in tissue renewal and regeneration, or fibrosis and degeneration.
TCs are essential to heart function through multiple interactions with cardiac progenitors, cardiomyocytes or other cardiac cells, but appreciation of their contribution has too suffered from the incomplete characterization of their molecular identity. CD34 and PDGFRα have been most widely used to describe TCs in various tissues, organs, in physiological and pathological conditions, but these markers are not highly-specific. Lately, FOXL1+ TCs have been showed to compartmentalize the production of Wnt ligands and inhibitors and to enable localized pathway activation favoring intestinal epithelium renewal. FOXL1 seems to be a reliable marker for TCs as a subset of PDGFRα+ cells in the intestine and we will investigate if it can also be used for TCs of the heart. Using transgenic mice, expressing fluorescent reporters or Cre-recombinase, advanced microscopy techniques (such as correlative light-electron microscopy and super-resolution microscopy) and isolation methods, we will investigate the TC transcriptome and proteome to find a marker of identity.
Objectives: To generate an unbiased molecular profile of cardiac TCs, and to determine their contribution to myocardial development.
identification of a specific marker for the cardiac TCs,
development of a workflow for TC isolation from the cardiac tissue,
analysis of the TC transcriptome in heart development.