Emerging diverse roles of telocytes

Abstract

Since the first description of 'interstitial cells of Cajal' in the mammalian gut in 1911, scientists have found structurally similar cells, now termed telocytes, in numerous tissues throughout the body. These cells have recently sparked renewed interest, facilitated through the development of a molecular handle to genetically manipulate their function in tissue homeostasis and disease. In this Primer, we discuss the discovery of telocytes, their physical properties, distribution and function, focusing on recent developments in the functional analysis of Foxl1-positive telocytes in the intestinal stem cell niche, and, finally, the current challenges of studying telocytes as a distinct cell type.

Keywords: Stem cell niche; Stroma; Telocyte.

Fig. 1.

TEM images of telocytes in vivo. (A-C) Telocytes can be seen with small cell bodies and long cytoplasmic processes that interact with each other and other surrounding cells in the exocrine pancreas (A,B) or epicardium (C). In the human exocrine pancreas, telocytes are highlighted in blue and form networks around acini, mast cells and blood capillaries. CMP, cardiomycyte progenitors; TC, telocyte; Tp, telopode; MC, mast cell; ICLC(p), Interstitial Cajal-like cell (processes). Reprinted with permission from Nicolescu and Popescu, 2012 and Popescu et al., 2009.

Fig. 2.

Three-dimensional reconstruction of a human skin telocyte. Focused ion beam scanning electron microscopy (FIB-SEM) tomography of a human skin telocyte (blue) shows ribbon-like telopodes, different from the ‘moniliform’ structure used to describe physical features of telocytes. In purple are extracellular vesicles, possibly budded from the telocyte and proposed to play a role in cell-cell signaling with neighboring cells. TC, telocyte; Tp, telopode. Reprinted with permission from Cretoiu et al., 2015.

Fig. 3.

Intestinal subepithelial telocytes provide Wnt signaling to the epithelium. (A) Lightsheet imaging of cleared mouse whole small intestine using X-CLARITY. Immunofluorescent staining for PDGFRα (green) and EpCAM (red) showing the subepithelial network of FOXL1-/PDGFRα-positive telocytes. Reprinted with permission from Shoshkes-Carmel et al., 2018. (B) The small intestinal epithelium consists of the crypt, which houses intestinal stem cells and transit amplifying cells, and the villus, which consists of the mature enterocytes and secretory cells. FOXL1-expressing telocytes lie just beneath the epithelium, forming a continuous plexus. Telocytes beneath the small intestinal epithelium secrete Wnt, BMP and R-spondin proteins at specific positions along the crypt-villus axis to limit Wnt activity to LGR5-expressing stem cells and transit amplifying cells. Blue wedges represent expression gradents.