FOXO3 promotes quiescence in adult muscle stem cells during the process of self-renewal.
FOXO3 promotes quiescence in adult muscle stem cells during the process of self-renewal.
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DOI：
10.1016/j.stemcr.2014.02.002
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发表时间：
2014-04-08
影响因子：
5.9
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
Gopinath, Suchitra D.;Webb, Ashley E.;Brunet, Anne;Rando, Thomas A.
骨骼肌干细胞或“卫星细胞”（SC）是受损肌肉组织再生所必需的。虽然SC在再生过程中自我更新，但SC重新进入静止状态的机制仍然难以捉摸。我们发现，FOXO 3，叉头家族的转录因子的成员，在静止的SC（QSC）中表达。QSC中Foxo3的条件性缺失损害自我更新并增加SC采用分化命运的倾向。缺乏FOXO3的SC的转录分析揭示了Notch信号传导的下调，Notch信号传导是SC静止的关键调节因子。相反，Notch胞内结构域（NICD）的过表达挽救了FOXO 3缺陷型SC的自我更新缺陷。我们发现FOXO 3调节NOTCH 1和NOTCH 3受体的表达，并且减少NOTCH 1和NOTCH 3受体的表达表型模仿了FOXO 3缺乏在SC中的作用。我们证明FOXO 3可能通过激活Notch信号传导，促进成人肌肉再生中SC自我更新期间的静止状态。FOXO 3在静止的成体干细胞中表达FOXO 3是干细胞自我更新所必需的FOXO 3缺陷的干细胞表现出更高的分化倾向FOXO 3促进Notch信号传导，Notch信号传导是成体干细胞静止的关键调节因子关于控制肌肉干细胞自我更新的分子机制知之甚少。Rando及其同事表明，FOXO 3是一种叉头家族转录因子，它激活Notch信号传导，这是肌肉干细胞静止状态的关键调节因子，从而促进肌肉再生过程中的自我更新。
Skeletal muscle stem cells, or “satellite cells” (SCs), are required for the regeneration of damaged muscle tissue. Although SCs self-renew during regeneration, the mechanisms that govern SC re-entry into quiescence remain elusive. We show that FOXO3, a member of the forkhead family of transcription factors, is expressed in quiescent SCs (QSCs). Conditional deletion of Foxo3 in QSCs impairs self-renewal and increases the propensity of SCs to adopt a differentiated fate. Transcriptional analysis of SCs lacking FOXO3 revealed a downregulation of Notch signaling, a key regulator of SC quiescence. Conversely, overexpression of Notch intracellular domain (NICD) rescued the self-renewal deficit of FOXO3-deficient SCs. We show that FOXO3 regulates NOTCH1 and NOTCH3 receptor expression and that decreasing expression of NOTCH1 and NOTCH3 receptors phenocopies the effect of FOXO3 deficiency in SCs. We demonstrate that FOXO3, perhaps by activating Notch signaling, promotes the quiescent state during SC self-renewal in adult muscle regeneration. FOXO3 is expressed in quiescent adult SCs FOXO3 is required for self-renewal of SCs FOXO3-deficient SCs display an increased propensity to differentiate FOXO3 promotes Notch signaling, a key regulator of quiescence in adult SCs Little is known about the molecular mechanisms that govern muscle stem cell self-renewal. Rando and colleagues show that FOXO3, a forkhead family transcription factor, activates Notch signaling, a key regulator of the quiescent state in muscle stem cells, and thereby promotes self-renewal during muscle regeneration.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
3.9
作者：
Lam, E. W-F.;Francis, R. E.;Petkovic, M.
通讯作者：
Petkovic, M.
DOI：
10.1111/j.1748-1716.1987.tb08144.x
发表时间：
1987-06-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
JENNISCHE, E;HANSSON, HA
通讯作者：
HANSSON, HA
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
5.1
作者：
Heslop, L;Beauchamp, JR;Zammit, PS
通讯作者：
Zammit, PS