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. 2021 Feb 18:9:631272.
doi: 10.3389/fcell.2021.631272. eCollection 2021.

Tendon Stem/Progenitor Cell Subpopulations and Their Implications in Tendon Biology

Zizhan Huang  1   2   3 , Zi Yin  3   4   5 , Jialu Xu  6 , Yang Fei  1   2   3 , Boon Chin Heng  7 , Xuesheng Jiang  8 , Weishan Chen  1   2 , Weiliang Shen  1   2   3   4   5
Affiliations

Tendon Stem/Progenitor Cell Subpopulations and Their Implications in Tendon Biology

Zizhan Huang et al. Front Cell Dev Biol. .

Abstract

Tendon harbors a cell population that possesses stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity, commonly referred to as tendon stem/progenitor cells (TSPCs). Various techniques have been employed to study how TSPCs are implicated in tendon development, homeostasis and healing. Recent advances in single-cell analysis have enabled much progress in identifying and characterizing distinct subpopulations of TSPCs, which provides a more comprehensive view of TSPCs function in tendon biology. Understanding the mechanisms of physiological and pathological processes regulated by TSPCs, especially a particular subpopulation, would greatly benefit treatment of diseased tendons. Here, we summarize the current scientific literature on the various subpopulations of TSPCs, and discuss how TSPCs can contribute to tissue homeostasis and pathogenesis, as well as examine the key modulatory signaling pathways that determine stem/progenitor cell state. A better understanding of the roles that TSPCs play in tendon biology may facilitate the development of novel treatment strategies for tendon diseases.

Keywords: TGFβ; healing; niche; subpopulation; tendon stem/progenitor cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of tendon hierarchical structure and various subpopulations of TSPCs with specific markers harvested from different niches, including tendon proper, peritenon and perivascular region. Tenocytes are aligned between fibers. It should be noted that some of these subpopulations might overlap with each other and perivascular TSPCs may be present in endotenon as well as the peritenon. What’s more, the exact location of proper-derived TSPCs is not well determined. Figures were produced using Servier Medical Art (https://smart.servier.com/).
FIGURE 2
FIGURE 2
Schematic representation of how TSPCs are implicated in tendon homeostasis and regeneration. TSPCs remain mostly dormant in homeostatic state and surrounding non-stem/progenitor cells could secret factors to regulate their differentiation. Upon injury, TSPCs would be activated and mobilized. TSPCs self-renew, proliferate, migrate to the lesion and differentiate into tenocytes as well as modify the inflammatory process by increasing regulatory molecules such as IL-10. Figures were produced using Servier Medical Art (https://smart.servier.com/).
FIGURE 3
FIGURE 3
Schematic representation of the complex regulatory roles of the TGFβ superfamily in TSPCs. TGFβ signaling has been shown to maintain the differentiated fate of tenocytes, without which tenocytes would revert to a more TSPC-like state. TGFβ signaling directs distinct lineage commitment of TSPCs by different mechanisms. BMP signaling contributes to erroneous differentiation of TSPCs. TGFβ superfamily members, including TGFβ signaling, BMP signaling, and GDF signaling are all vital in defining the fate of tendon progenitors during tendon formation. Figures were produced using Servier Medical Art (https://smart.servier.com/).
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