Telocytes transfer extracellular vesicles loaded with microRNAs to stem cells

Telocytes (TCs) are cells ubiquitously distributed in the body and characterized by very long and thin prolongations named telopodes (Tps). Cardiac TCs are the best characterized TCs for the moment. Tps release extracellular vesicles (EVs) in vivo and in vitro suggesting that TCs regulate the activity of other cells by vesicular paracrine signals. TCs have been found within the stem cell niche of several organs. Electron microscopy or electron tomography has shown that Tps are located in close vicinity of stem cells (SC). Since stem cell regulation by niche components involves paracrine signalling, we have investigated if TCs could be part of this mechanism. Using fluorescent labelling of cells and EVs with calcein and Cy5-miR-21 oligos, we provide evidence that TCs can modulate SC through EVs loaded with microRNAs. TCs deliver microRNA to cardiac stem cells (CSCs), as well as to other types of SCs (e.g. hematopoietic SC) indicating that this mechanism is not restricted to cardiac tissue. We also found that CSCs deliver microRNA loaded EVs to TCs, suggesting that there is a continuous, post-transcriptional regulatory signal back and forth between TCs and SC. In conclusion, our data reveal the existence of a reciprocal (bidirectional) epigenetic signalling between TCs and SC.