The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53.
The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53.
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DOI：
10.1016/j.stemcr.2018.01.007
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发表时间：
2018-03-13
影响因子：
5.9
通讯作者：
Pisconti A
中科院分区：
文献类型：
--
作者：
Flamini V;Ghadiali RS;Antczak P;Rothwell A;Turnbull JE;Pisconti A
卫星细胞是成体肌肉干细胞，存在于调节自身稳态的特殊环境中。在卫星细胞来源的成肌细胞中，小生境产生的信号如何整合来调节基因表达还知之甚少。我们采取了一种无偏见的方法来研究卫星细胞生态位对卫星细胞来源的成肌细胞转录调控的影响，并确定肿瘤抑制基因P53在调节成肌细胞静止的过程中起关键作用。在激活和增殖后，在壁龛存在的情况下培养的成肌细胞亚群上调P53并无法分化。当在体外储备细胞实验中模拟卫星细胞的自我更新时，用Nutlin-3处理的成肌细胞无法分化，反而变得静止。Nutlin-3增加了细胞中的p53水平。由于这两种Nutlin-3效应都被小干扰RNA介导的P53基因敲除所拯救，我们得出结论，严格控制成肌细胞中的P53水平调节分化和恢复静止之间的平衡。卫星细胞生态位驱动一个促进自我更新的转录程序。p53的不对称增加抑制了生态位相关的成肌细胞的分化。在本文中，Pisconi等人认为，P53的持续增加促进了静止，但以牺牲分化为代价。使用不偏不倚的方法来证明驱动成肌细胞命运转变的转录程序直接受周围生态位的性质调节。作者认为P53是一种小生境诱导的转录调节因子，当细胞周期退出时，成肌细胞亚群增加，以牺牲分化为代价促进静止。
Satellite cells are adult muscle stem cells residing in a specialized niche that regulates their homeostasis. How niche-generated signals integrate to regulate gene expression in satellite cell-derived myoblasts is poorly understood. We undertook an unbiased approach to study the effect of the satellite cell niche on satellite cell-derived myoblast transcriptional regulation and identified the tumor suppressor p53 as a key player in the regulation of myoblast quiescence. After activation and proliferation, a subpopulation of myoblasts cultured in the presence of the niche upregulates p53 and fails to differentiate. When satellite cell self-renewal is modeled ex vivo in a reserve cell assay, myoblasts treated with Nutlin-3, which increases p53 levels in the cell, fail to differentiate and instead become quiescent. Since both these Nutlin-3 effects are rescued by small interfering RNA-mediated p53 knockdown, we conclude that a tight control of p53 levels in myoblasts regulates the balance between differentiation and return to quiescence. The satellite cell niche drives a transcriptional program that promotes self-renewal An asymmetric increase in p53 inhibits differentiation in niche-associated myoblasts A sustained increase in p53 promotes quiescence at the expense of differentiation In this article, Pisconti et al. use an unbiased approach to show that the transcriptional program that drives myoblast cell fate transitions is directly regulated by the nature of the surrounding niche. The authors identify p53 as a niche-induced transcriptional regulator that increases in a subset of myoblasts upon cell-cycle exit, promoting quiescence at the expense of differentiation.
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DOI：
10.1083/jcb.151.6.1295
发表时间：
2000-12-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Porrello A;Cerone MA;Coen S;Gurtner A;Fontemaggi G;Cimino L;Piaggio G;Sacchi A;Soddu S
通讯作者：
Soddu S
影响因子：
5.9
作者：
Gopinath, Suchitra D.;Webb, Ashley E.;Brunet, Anne;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
影响因子：
2.7
作者：
Olguin, HC;Olwin, BB
通讯作者：
Olwin, BB
影响因子：
8
作者：
Sarker, KP;Lee, KY
通讯作者：
Lee, KY
DOI：
10.1006/bbrc.1993.1473
发表时间：
1993-04-30
影响因子：
3.1
作者：
HALEVY, O
通讯作者：
HALEVY, O