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首页> 外文期刊>Cell stem cell >Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest
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Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest

机译：肌肉干细胞在组织生长期间经历了广泛的克隆漂移，通过Meox1介导的G2细胞循环骤离诱导

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摘要

Organ growth requires a careful balance between stem cell self-renewal and lineage commitment to ensure proper tissue expansion. The cellular and molecular mechanisms that mediate this balance are unresolved in most organs, including skeletal muscle. Here we identify a long-lived stem cell pool that mediates growth of the zebrafish myotome. This population exhibits extensive clonal drift, shifting from randomdeployment of stem cells during development to reliance on a small number of dominant clones to fuel the vast majority of muscle growth. This clonal drift requires Meox1, a homeobox protein that directly inhibits the cell-cycle checkpoint gene ccnb1. Meox1 initiates G(2) cell-cycle arrest within muscle stem cells, and disrupting this G(2) arrest causes premature lineage commitment and the resulting defects in muscle growth. These findings reveal that distinct regulatory mechanisms orchestrate stem cell dynamics during organ growth, beyond the G(0)/G(1) cell-cycle inhibition traditionally associated with maintaining tissue-resident stem cells.
机译：器官生长需要仔细平衡干细胞自我更新和谱系承诺，以确保适当的组织扩张。介导这种平衡的细胞和分子机制在大多数器官中未得到解决，包括骨骼肌。在这里，我们鉴定了一种介导斑马鱼苗生长的长寿命的干细胞库。该人群表现出广泛的克隆漂移，从干细胞随机部署转移到开发期间，以依赖于少量显性克隆来促进绝大多数肌肉生长。该克隆漂移需要Meox1，一种Isoxox蛋白，可直接抑制细胞周期检查点基因CCNB1。 Meox1在肌肉干细胞内启动G（​​2）细胞周期停滞，扰乱该G（2）逮捕导致过早的血统承诺和肌肉生长中产生的缺陷。这些发现表明，不同的调节机制在器官生长期间协调干细胞动态，超出了传统上与维持组织静脉干细胞的G（0）/ g（1）细胞循环抑制。

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  • 来源
    《Cell stem cell》 |2017年第1期|共19页
  • 作者

    Phong Dang Nguyen; Gurevich David Baruch; Sonntag Carmen; Hersey Lucy; Alaei Sara; Nim Hieu Tri; Siegel Ashley; Hall Thomas Edward; Rossello Fernando Jaime; Boyd Sarah Elizabeth; Polo Jose Maria; Currie Peter David;

  • 作者单位

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

    Monash Univ Australian Regenerat Med Inst Level 1 15 Innovat Walk Wellington Rd Clayton Vic;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
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