Genetic comparison of mouse lung telocytes with mesenchymal stem cells and fibroblasts

Abstract

Telocytes (TCs) are interstitial cells with telopodes - very long prolongations that establish intercellular contacts with various types of cells. Telocytes have been found in many organs and various species and have been characterized ultrastructurally, immunophenotypically and electrophysiologically (www.telocytes.com). Telocytes are distributed through organ stroma forming a three-dimensional network in close contacts with blood vessels, nerve bundles and cells of the local immune system. Moreover, it has been shown that TCs express a broad range of microRNAs, such as pro-angiogenic and stromal-specific miRs. In this study, the gene expression profile of murine lung TCs is compared with other differentiated interstitial cells (fibroblasts) and with stromal stem/progenitor cells. More than 2000 and 4000 genes were found up- or down-regulated, respectively, in TCs as compared with either MSCs or fibroblasts. Several components or regulators of the vascular basement membrane are highly expressed in TCs, such as Nidogen, Collagen type IV and Tissue Inhibitor of Metalloproteinase 3 (TIMP3). Given that TCs locate in close vicinity of small vessels and capillaries, the data suggest the implication of TCs in vascular branching. Telocytes express also matrix metalloproteases Mmp3 and Mmp10, and thus could regulate extracellular matrix during vascular branching and de novo vessel formation. In conclusion, our data show that TCs are not fibroblasts, as the ultrastructure, immunocytochemistry and microRNA assay previously indicated. Gene expression profile demonstrates that TCs are functionally distinct interstitial cells with specific roles in cell signalling, tissue remodelling and angiogenesis.

Fig. 1

Hierarchical cluster analysis of the differentially expressed genes among telocytes (TCs), mesenchymal stem cells (MSCs) and fibroblasts (Fbs).

Fig. 2

Gene ontology of the genes with at least twofolds difference among telocytes (TCs), mesenchymal stem cells (MSCs) and fibroblast (Fbs), analysed under following categories: Biological Processes (A), Cellular Components (B) and Molecular Function (C). (P ≤ 0.01).

Fig. 3

String Network of the proteins that are differentially expressed among telocytes (TCs), mesenchymal stem cells (MSCs) and fibroblast (Fbs). A group of 46 genes are found connected functionally. Strong associations are represented by thick lines.