Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation

Yuki Yoshimoto, Akiyoshi Uezumi, Madoka Ikemoto-Uezumi, Kaori Tanaka, Xinyi Yu, Tamaki Kurosawa, Shinsei Yambe, Kazumitsu Maehara, Yasuyuki Ohkawa, Yusuke Sotomaru, Chisa Shukunami

    研究成果: ジャーナルへの寄稿学術誌査読

    4 被引用数 (Scopus)

    抄録

    The musculoskeletal system is integrated by tendons that are characterized by the expression of scleraxis (Scx), a functionally important transcription factor. Here, we newly developed a tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitoring fluorescence, which reflects a dynamic differentiation process. Among several developmentally relevant factors, transforming growth factor-beta 2 (TGF-β2) was the most potent inducer for differentiation of tenomodulin-expressing mature tenocytes. Single-cell RNA sequencing (scRNA-seq) revealed 11 distinct clusters, including mature tenocyte population and tenogenic differentiation trajectory, which recapitulated the in vivo developmental process. Analysis of the scRNA-seq dataset highlighted the importance of retinoic acid (RA) as a regulatory pathway of tenogenic differentiation. RA signaling was shown to have inhibitory effects on entheseal chondrogenic differentiation as well as TGF-β2-dependent tenogenic/fibrochondrogenic differentiation. The collective findings provide a new opportunity for tendon research and further insight into the mechanistic understanding of the differentiation pathway to a tenogenic fate.

    本文言語英語
    論文番号780038
    ジャーナルFrontiers in Cell and Developmental Biology
    10
    DOI
    出版ステータス出版済み - 3月 9 2022

    !!!All Science Journal Classification (ASJC) codes

    • 発生生物学
    • 細胞生物学

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