Telocytes: An Emerging Component of Stem Cell Niche Microenvironment

Abstract

Telocytes (TCs) are newly identified interstitial cells characterized by thin and long cytoplasmic processes, called telopodes, which exhibit a distinctive moniliform shape and, often, a sinuous trajectory. Telopodes typically organize in intricate networks within the stromal space of most organs, where they communicate with neighboring cells by means of specialized cell-to-cell junctions or shedding extracellular vesicles. Hence, TCs are generally regarded as supporting cells that help in the maintenance of local tissue homeostasis, with an ever-increasing number of studies trying to explore their functions both in physiological and pathological conditions. Notably, TCs appear to be part of stem cell (SC) niches in different organs, including the intestine, skeletal muscle, heart, lung, and skin. Indeed, growing evidence points toward a possible implication of TCs in the regulation of the activity of tissue-resident SCs and in shaping the SC niche microenvironment, thus contributing to tissue renewal and repair. Here, we review how the introduction of TCs into the scientific literature has deepened our knowledge of the stromal architecture focusing on the intestine and skeletal muscle, two organs in which the recently unveiled unique relationship between TCs and SCs is currently in the spotlight as potential target for tissue regenerative purposes.

Scleroderma-like Impairment in the Network of Telocytes/CD34+ Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis

“…In such a scenario, the relatively recent discovery of telocytes (TCs) as a distinctive cell type populating the stromal compartment of the skin and other organs added further complexity to fibroblast heterogeneity [3][4][5][6][7][8]. Indeed, a significant body of evidence accumulated over the last decade indicates that TCs are ultrastructurally and immunophenotypically different from 'classical' fibroblasts [3,4,[8][9][10].…”

“…In particular, TCs are distinguishable by transmission electron microscopy (TEM) as stromal cells with telopodes, which are extremely long cytoplasmic processes with a moniliform profile due to the alternation of very slender segments (podomers) and small dilated portions (podoms) [3,4,11,12]. When instead studying TCs by light microscopy using immunohistochemical techniques, it must be kept in mind that currently TC-specific antigens have yet to be identified, and that their antigenic profiles can vary according to the tissue/organ considered [4,6,7,13]. Nevertheless, at almost every anatomical site in which they have been identified, TCs appear to express CD34, which led to the widely accepted definition of TCs/CD34 + stromal cells [6,8,10,14].…”

“…When instead studying TCs by light microscopy using immunohistochemical techniques, it must be kept in mind that currently TC-specific antigens have yet to be identified, and that their antigenic profiles can vary according to the tissue/organ considered [4,6,7,13]. Nevertheless, at almost every anatomical site in which they have been identified, TCs appear to express CD34, which led to the widely accepted definition of TCs/CD34 + stromal cells [6,8,10,14]. In general, TCs/CD34 + stromal cells are spatially arranged with their telopodes forming a scaffold-like interstitial network, which is thought to provide support to neighboring cells through both intercellular contacts and transfer of extracellular vesicles carrying molecular signals as various as cytokines, growth factors, mRNAs, and epigenetic regulators such as miRNAs and other non-coding RNAs [3,4,7,15].…”

Cardiac Telocytes 16 Years on—What Have We Learned So Far, and How Close Are We to Routine Application of the Knowledge in Cardiovascular Regenerative Medicine?

“…In addition to the direct communication via heterocellular junctions with other cells, epicardial TCs were also demonstrated to shed extracellular vesicles containing bioactive molecules, through which TCs may influence their surroundings in a paracrine manner [39]. It is important to note that TCs were also identified in stem-cell niches of other organs, including the gut, skeletal muscle, lung, and skin [40]. A significantly underresearched component of the epicardium is the epicardial white adipose tissue.…”

Identifying key regulators of the intestinal stem cell niche

“…Mechanisms that regulate proliferation, apoptosis, migration and differentiation of intestinal epithelial cells have been well characterised, however, questions still remain as to how all of these processes are co-ordinated to achieve equilibrium during the perpetual state of epithelial cell renewal observed in the intestine. Factors that control the ISC niche are produced by ISCs themselves, neighbouring Paneth cells and specialised sub-epithelial mesenchymal cells including pericryptal myofibroblasts, telocytes, newly identified trophocytes and immune cells [ 10–12 ]. Additional non-cellular components of the ISC niche include the basement membrane matrix.…”