A Cd9+Cd271+ stem/progenitor population and the SHP2 pathway contribute to neonatal-to-adult switching that regulates tendon maturation

• Published in: Cell reports (Cambridge) Vol. 39; no. 4; p. 110762
• Main Authors: Fan, Chunmei, Zhao, Yanyan, Chen, Yangwu, Qin, Tian, Lin, Junxin, Han, Shan, Yan, Ruojin, Lei, Tingyun, Xie, Yuanhao, Wang, Tingzhang, Gu, Shen, Ouyang, Hongwei, Shen, Weiliang, Yin, Zi, Chen, Xiao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.04.2022
• Subjects: Adapalene - metabolism; Animals; Cell Differentiation; collagen fibrils; Mice; nerve growth factor; Shp2; Signal Transduction - physiology; single-cell RNA sequence; Stem Cells - metabolism; tendon maturation; tendon regeneration; tendon stem/progenitor cells; Tendons; Shp2; nerve growth factor; tendon maturation; collagen fibrils; CP: Developmental biology; tendon regeneration; single-cell RNA sequence; tendon stem/progenitor cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110762

Tendon maturation lays the foundation for postnatal tendon development, its proper mechanical function, and regeneration, but the critical cell populations and the entangled mechanisms remain poorly understood. Here, by integrating the structural, mechanical, and molecular properties, we show that post-natal days 7–14 are the crucial transitional stage for mouse tendon maturation. We decode the cellular and molecular regulatory networks at the single-cell level. We find that a nerve growth factor (NGF)-secreting Cd9+Cd271+ tendon stem/progenitor cell population mainly prompts conversion from neonate to adult tendon. Through single-cell gene regulatory network analysis, in vitro inhibitor identification, and in vivo tendon-specific Shp2 deletion, we find that SHP2 signaling is a regulator for tendon maturation. Our research comprehensively reveals the dynamic cell population transition during tendon maturation, implementing insights into the critical roles of the maturation-related stem cell population and SHP2 signaling pathway during tendon differentiation and regeneration. [Display omitted] •Systematically evaluate the critical transitional stage for tendon maturation•Uncover convergence of cell identities during tendon maturation•An NGF-secreting Cd9+Cd271+ TSPC mediates the transition•NGF/SHP2 pathway regulates tendon maturation Fan et al. uncovered the cellular and molecular regulatory network during tendon maturation at single-cell resolution. They identify a Cd9+Cd271+ stem/progenitor population and the NGF/SHP2 pathway that regulate the transition from nascent to mature tendons.