Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo.
Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo.
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DOI：
10.1016/j.stemcr.2021.11.012
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发表时间：
2022-01-11
影响因子：
5.9
通讯作者：
Rando TA
中科院分区：
文献类型：
--
作者：
Arjona M;Goshayeshi A;Rodriguez-Mateo C;Brett JO;Both P;Ishak H;Rando TA
成体骨骼肌干细胞 (MuSC) 对于肌肉再生很重要，是细胞治疗的潜在来源。然而，分离后，MuSC 迅速退出静止状态并失去移植效力。体外维持静止状态可以保持 MuSC 移植效率，并提供研究静止生物学的机会。在这里，我们证明图巴他汀 A (TubA) 是一种 Hdac6 抑制剂，可防止初级纤毛吸收、维持静止并增强 MuSC 离体存活。 TubA 处理的细胞的表型表征和转录组分析表明，TubA 保持了静止的大部分生物学特征和分子特征。此外，TubA 处理的 MuSC 在移植后表现出改善的植入能力。 TubA 还诱导循环 MuSC 恢复静止并改善植入，揭示了 MuSC 治疗的潜在扩展应用。总而言之，这些研究证明了 TubA 能够维持 MuSC 离体静止并增强 MuSC 及其后代的治疗潜力。 TubA 可防止原发性纤毛吸收并维持 MuSC 离体静止状态 TubA 处理可维持静止 MuSC 的转录特征 TubA 处理可维持 MuSC 移植研究的植入潜力 TubA 诱导循环 MuSC 后代恢复静止状态表明 TubA（一种 HDAC6 抑制剂）可以抑制原发性纤毛吸收并保持 MuSC 静息和离体干细胞效力。事实上，TubA 治疗可以维持 MuSC 的植入潜力，并诱导循环 MuSC 恢复静止状态，这揭示了一种增强 MuSC 治疗潜力的潜在有价值的方法。
Adult skeletal muscle stem cells (MuSCs) are important for muscle regeneration and constitute a potential source of cell therapy. However, upon isolation, MuSCs rapidly exit quiescence and lose transplantation potency. Maintenance of the quiescent state in vitro preserves MuSC transplantation efficiency and provides an opportunity to study the biology of quiescence. Here we show that Tubastatin A (TubA), an Hdac6 inhibitor, prevents primary cilium resorption, maintains quiescence, and enhances MuSC survival ex vivo. Phenotypic characterization and transcriptomic analysis of TubA-treated cells revealed that TubA maintains most of the biological features and molecular signatures of quiescence. Furthermore, TubA-treated MuSCs showed improved engraftment ability upon transplantation. TubA also induced a return to quiescence and improved engraftment of cycling MuSCs, revealing a potentially expanded application for MuSC therapeutics. Altogether, these studies demonstrate the ability of TubA to maintain MuSC quiescence ex vivo and to enhance the therapeutic potential of MuSCs and their progeny. TubA prevents primary cilium resorption and maintains MuSC quiescence ex vivo TubA treatment maintains the transcriptional characteristics of quiescent MuSCs Treatment with TubA sustains MuSC engraftment potential for transplantation studies TubA induces a return to quiescence of cycling MuSC progeny In this article, Arjona et al. show that TubA, an HDAC6 inhibitor, can inhibit primary cilium resorption and preserve MuSC quiescence and stem cell potency ex vivo. Indeed, treatment with TubA maintains MuSC engraftment potential and induces a return to quiescence in cycling MuSCs, revealing a potentially valuable approach to enhancing the therapeutic potential of MuSCs.
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DOI：
10.1016/j.bbrc.2015.04.028
发表时间：
2015-05-22
影响因子：
3.1
作者：
Hong, Hyowon;Kim, Jongshin;Kim, Joon
通讯作者：
Kim, Joon
影响因子：
4.6
作者：
Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
通讯作者：
Fan, Chen-Ming
影响因子：
12.4
作者：
Ikemoto, Madoka;Fukada, So-ichiro;Takeda, Shin'ichi
通讯作者：
Takeda, Shin'ichi
DOI：
10.1038/nrm3591
发表时间：
2013-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM