间充质祖细胞和肌肉干细胞间信号传递确保干细胞对机械负荷适应性反应
2021-12-05   阅读:518   来源:细胞

日本大阪大学So-ichiro Fukada、东京都老人综合研究所Akiyoshi Uezumi等研究人员合作发现,间充质祖细胞和肌肉干细胞之间的信号传递确保干细胞对机械负荷的适应性反应。相关论文于2021年12月1日在线发表在《细胞—干细胞》杂志上。

研究人员证明了间质祖细胞对机械负荷的反应,并在一个增加肌肉负荷的外科小鼠模型中刺激了肌肉干细胞(MuSC)的增殖。从机制上讲,间质祖细胞中Yes相关蛋白1(Yap1)/具有PDZ结合模体的转录辅助因子(Taz)的转录激活导致凝血栓蛋白-1(Thbs1)的局部产生,这又通过CD47信号驱动MuSC增殖。然而,在平衡条件下,CD47信号传导不足以促进MuSC的增殖,而是取决于降钙素受体的事先下调。这些研究结果表明,间质祖细胞和MuSC之间通过Yap1/Taz-Thbs1-CD47途径的传播信号是在肌肉肥大期间建立MuSC供应的关键。

据悉,适应机械负荷,导致力量和功率输出增强,是骨骼肌的一个特征。高效肌肉肥大所需的新肌核形成依赖于MuSC的事先激活和增殖。然而,在增加负荷的条件下,控制MuSC扩张的机制并不完全了解。

附:英文原文

Title: Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load

Author: Akihiro Kaneshige, Takayuki Kaji, Lidan Zhang, Hayato Saito, Ayasa Nakamura, Tamaki Kurosawa, Madoka Ikemoto-Uezumi, Kazutake Tsujikawa, Shigeto Seno, Masatoshi Hori, Yasuyuki Saito, Takashi Matozaki, Kazumitsu Maehara, Yasuyuki Ohkawa, Michael Potente, Shuichi Watanabe, Thomas Braun, Akiyoshi Uezumi, So-ichiro Fukada

Issue&Volume: 2021-12-01

Abstract: Adaptation to mechanical load, leading to enhanced force and power output, is a characteristic feature of skeletal muscle. Formation of new myonuclei required for efficient muscle hypertrophy relies on prior activation and proliferation of muscle stem cells (MuSCs). However, the mechanisms controlling MuSC expansion under conditions of increased load are not fully understood. Here we demonstrate that interstitial mesenchymal progenitors respond to mechanical load and stimulate MuSC proliferation in a surgical mouse model of increased muscle load. Mechanistically, transcriptional activation of Yes-associated protein 1 (Yap1)/transcriptional coactivator with PDZ-binding motif (Taz) in mesenchymal progenitors results in local production of thrombospondin-1 (Thbs1), which, in turn, drives MuSC proliferation through CD47 signaling. Under homeostatic conditions, however, CD47 signaling is insufficient to promote MuSC proliferation and instead depends on prior downregulation of the Calcitonin receptor. Our results suggest that relayed signaling between mesenchymal progenitors and MuSCs through a Yap1/Taz-Thbs1-CD47 pathway is critical to establish the supply of MuSCs during muscle hypertrophy.

DOI: 10.1016/j.stem.2021.11.003

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