ULTRASTRUCTURAL PATHOLOGY AND BIOIMAGING LAB

TELOCYTE IDENTITY – A DISTINCT CELL OR A DIFFERENT PHENOTYPE?

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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

Funding: 1,198,032 RON

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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.

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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.

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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 shown 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.

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Objective: To generate an unbiased molecular profile of cardiac TCs, and to determine their contribution to myocardial development.

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Expected results:

• 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.