Transiently active Wnt/β-catenin signaling is not required but must be silenced for stem cell function during muscle regeneration.
Transiently active Wnt/β-catenin signaling is not required but must be silenced for stem cell function during muscle regeneration.
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DOI：
10.1016/j.stemcr.2014.06.019
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发表时间：
2014-09-09
影响因子：
5.9
通讯作者：
Kardon, Gabrielle
中科院分区：
文献类型：
--
作者：
Murphy, Malea M.;Keefe, Alexandra C.;Lawson, Jennifer A.;Flygare, Steven D.;Yandell, Mark;Kardon, Gabrielle
成人肌肉的再生能力是由肌肉干细胞介导的，称为卫星细胞。与许多干细胞一样，Wnt/β-catenin信号传导已被提出在再生期间在卫星细胞中是关键的。使用新的遗传试剂，我们明确地在体内测试Wnt/β-catenin信号传导是否是卫星细胞及其衍生物再生所必需和充分的。我们发现信号在过渡放大成肌细胞中短暂活跃，但不是再生或卫星细胞自我更新所需的。相反，瞬时激活的β-连环蛋白的下调对于限制再生反应是重要的，因为连续再生是有害的。成年卫星细胞中的Wnt/β-连环蛋白激活可能只是其发育谱系的遗迹，其中β-连环蛋白信号传导对胎儿肌发生至关重要。令人惊讶的是，在成人中，我们发现Wnt/β-catenin信号转导的沉默而不是激活对肌肉再生很重要。Wnt/β-catenin信号在肌肉再生过程中在成肌细胞中是短暂活跃的β-catenin在肌肉再生的肌原细胞中是不需要的β-catenin信号必须被沉默以限制再生反应β-catenin的需求和敏感性在胎儿和成人肌肉干细胞中的不同在这篇文章中，Kardon及其同事表明，Wnt/β-catenin信号在过渡扩增成肌细胞中是短暂活跃的，但不是再生或卫星细胞自我更新所必需的。相反，瞬时激活的β-连环蛋白的下调对于限制再生反应是重要的，因为连续再生是有害的。成年卫星细胞中的Wnt/β-catenin激活可能只是其发育谱系的遗迹。
Adult muscle’s exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/β-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/β-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which β-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/β-catenin signaling that is important for muscle regeneration. Wnt/β-catenin signaling is transiently active in myoblasts during muscle regeneration β-catenin is not required in myogenic cells for muscle regeneration β-catenin signaling in myoblasts must be silenced to limit the regenerative response β-catenin requirement and sensitivity differs in fetal and adult muscle stem cells In this article, Kardon and colleagues show that Wnt/β-catenin signaling is transiently active in transit-amplifying myoblasts but nevertheless is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage.
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DOI：
10.1083/jcb.200508001
发表时间：
2006-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kuang S;Chargé SB;Seale P;Huh M;Rudnicki MA
通讯作者：
Rudnicki MA
脊椎动物肢体肌肉的起源：祖细胞和肌细胞种群的作用。
影响因子：
--
作者：
Murphy M;Kardon G
通讯作者：
Kardon G
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：
7.5
作者：
Holland, Jane D.;Klaus, Alexandra;Birchmeier, Walter
通讯作者：
Birchmeier, Walter
DOI：
10.1098/rspb.1979.0086
发表时间：
1979-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GOULD, SJ;LEWONTIN, RC
通讯作者：
LEWONTIN, RC