Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation
Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation
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如果缺乏 Talpid3（初级纤毛形成所需的基因），肌肉干细胞功能就会受损
DOI：
10.1101/2022.10.14.512102
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Martinez-Heredia V
中科院分区：
文献类型：
--
作者：
Martinez-Heredia V
骨骼肌干细胞（MuSC）对于组织的稳态和损伤后的修复至关重要。在激活后，它们增殖以产生分化的成肌细胞。一部分细胞自我更新，重新进入肌纤维外基底层下的MuSC龛，并变得静止。静止期的MuSC具有初级纤毛，进入细胞周期后纤毛解体，离体实验表明纤毛对MuSC的自我更新很重要，但其在体内肌肉再生中的作用尚不清楚。Talpid 3（TA 3）是初级纤毛形成和Hedgehog（Hh）信号传导所必需的。在这里，我们使用他莫昔芬诱导的条件性删除TA 3的MuSC（iSC-KO），并显示再生受损的细胞毒性损伤。重复损伤加剧了TA 3 iSC-KO小鼠的再生表型，表明MuSC的耗竭。从肌纤维分离的MuSC后代的单细胞转录组学鉴定了几种信号传导途径的组分，其在不存在TA 3的情况下被失调，包括Hh和Wnt。Wnt的药理学激活恢复肌肉再生，而Purmorphamine，一种Hh途径中Smoothened（Smo）辅助受体的激活剂，没有作用。总之，我们的数据表明，TA 3和初级纤毛是重要的MuSC自我更新，药物治疗可以有效地恢复肌肉再生。
Skeletal muscle stem cells (MuSC) are crucial for tissue homeostasis and repair after injury. Following activation, they proliferate to generate differentiating myoblasts. A proportion of cells selfrenew, re-enter the MuSC niche under the basal lamina outside the myofiber and become quiescent. Quiescent MuSC have a primary cilium, which is disassembled upon cell cycle entry.Ex vivoexperiments suggest cilia are important for MuSC self-renewal, however, their role in muscle regenerationin vivoremains poorly understood. Talpid3 (TA3) is essential for primary cilia formation and Hedgehog (Hh) signalling. Here we use tamoxifen-inducible conditional deletion of TA3in MuSC (iSC-KO) and show that regeneration is impaired in response to cytotoxic injury. Repeat injury exacerbates the regeneration phenotype in TA3iSC-KOmice, indicating depletion of MuSCs. Single cell transcriptomics of MuSC progeny isolated from myofibers identifies components of several signalling pathways, which are deregulated in absence of TA3, including Hh and Wnt. Pharmacological activation of Wnt restores muscle regeneration, while purmorphamine, an activator of the Smoothened (Smo) co-receptor in the Hh pathway, has no effect. Together, our data suggest that TA3and primary cilia are important for MuSC self-renewal, and that pharmacological treatment can efficiently restore muscle regeneration.
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影响因子：
23.9
作者：
Guenther, Stefan;Kim, Johnny;Kostin, Sawa;Lepper, Christoph;Fan, Chen-Ming;Braun, Thomas
通讯作者：
Braun, Thomas
影响因子：
4.6
作者：
A. Borycki;A. Brown;C. Emerson
通讯作者：
A. Borycki;A. Brown;C. Emerson
原发纤毛：干细胞谱系规范的控制中心和细胞疗法的潜在目标
DOI：
--
发表时间：
2016
期刊：
影响因子：
--
作者：
J. Bodle;E. Loboa;E. Loboa
通讯作者：
E. Loboa
影响因子：
5.9
作者：
Murphy, Malea M.;Keefe, Alexandra C.;Lawson, Jennifer A.;Flygare, Steven D.;Yandell, Mark;Kardon, Gabrielle
通讯作者：
Kardon, Gabrielle
影响因子：
8.8
作者：
Machado, Leo;de Lima, Joana Esteves;Mourikis, Philippos
通讯作者：
Mourikis, Philippos