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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity
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The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity

机译：RNA结合蛋白Musashi本质上是维持干细胞身份所必需的

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摘要

A key goal of regenerative medicine is an understanding of the genetic factors that define the properties of stem cells. However, stem cell research in mammalian tissue has been hampered by a paucity of stem cell-specific markers. Although increasing evidence suggests that members of the Musashi (Msi) family of RNA-binding proteins play important functions in progenitor cells, it remains unclear whether there is a stem cell-autonomous requirement for Msi because of an inability to distinguish stem cells from early-lineage cells in mammalian tissues. Here, using the Drosophila testis as a model system for the study of stem cell regulation, we show specific evidence for a cell-autonomous requirement for Msi family proteins in regulating stem cell differentiation, leading to the identification of an RNA-binding protein required for sper-matogonial stem cell maintenance. We found that loss of Msi function disrupts the balance between germ-line stem cell renewal and differentiation, resulting in the premature differentiation of germ-line stem cells. Moreover, we found that, although Msi is expressed in both somatic and germ cells, Msi function is required intrinsically in stem cells for maintenance of stem cell identity. We also discovered a requirement for Msi function in male meiosis, revealing that Msi has distinct roles at different stages of germ cell differentiation. We describe the complementary expression patterns of the murine Msi paralogues Msi1 and Msi2 during sper-matogenesis, which support the idea of distinct, evolutionarily conserved roles of Msi.
机译：再生医学的一个关键目标是了解定义干细胞特性的遗传因素。但是，由于缺乏干细胞特异性标记物，哺乳动物组织中的干细胞研究受到了阻碍。尽管越来越多的证据表明，武藏（Msi）家族的RNA结合蛋白家族成员在祖细胞中起着重要的作用，但由于无法区分干细胞和早期的干细胞，目前尚不清楚Msi是否具有干细胞自治的需求。哺乳动物组织中的血统细胞。在这里，使用果蝇睾丸作为研究干细胞调节的模型系统，我们显示了Msi家族蛋白在调节干细胞分化中对细胞自主性需求的具体证据，从而鉴定了所需的RNA结合蛋白。精原干细胞的维护。我们发现，Msi功能丧失会破坏种系干细胞更新与分化之间的平衡，从而导致种系干细胞的过早分化。此外，我们发现，尽管Msi在体细胞和生殖细胞中均表达，但Msi功能本质上是干细胞中固有的，以维持干细胞的身份。我们还发现雄性减数分裂中Msi功能的需求，揭示了Msi在生殖细胞分化的不同阶段具有独特的作用。我们描述了精子发生过程中小鼠Msi旁系Msi1和Msi2的互补表达模式，这支持了Msi不同，进化上保守的作用的想法。

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