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首页> 外文期刊>Molecular and Cellular Biology >The Nuclear Receptor TLX Is Required for Gliomagenesis within the Adult Neurogenic Niche
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The Nuclear Receptor TLX Is Required for Gliomagenesis within the Adult Neurogenic Niche

机译：成年神经源性利基内胶质瘤的形成需要核受体TLX。

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Neural stem cells (NSCs) continually generate functional neurons in the adult brain. Due to their ability to proliferate, deregulated NSCs or their progenitors have been proposed as the cells of origin for a number of primary central nervous system neoplasms, including infiltrating gliomas. The orphan nuclear receptor TLX is required for proliferation of adult NSCs, and its upregulation promotes brain tumor formation. However, it is unknown whether TLX is required for gliomagenesis. We examined the genetic interactions between TLX and several tumor suppressors, as well as the role of TLX-dependent NSCs during gliomagenesis, using mouse models. Here, we show that TLX is essential for the proliferation of adult NSCs with a single deletion of p21, p53, or Pten or combined deletion of Pten and p53. While brain tumors still form in Tlx mutant mice, these tumors are less infiltrative and rarely associate with the adult neurogenic niches, suggesting a non-stem-cell origin. Taken together, these results indicate a critical role for TLX in NSC-dependent gliomagenesis and implicate TLX as a therapeutic target to inhibit the development of NSC-derived brain tumors.
机译：神经干细胞（NSC）在成年大脑中持续生成功能性神经元。由于它们的增殖能力，已提出去调节的NSCs或其祖细胞作为许多原发性中枢神经系统肿瘤包括浸润性神经胶质瘤的起源细胞。孤核受体TLX是成人NSC增殖所必需的，其上调促进了脑肿瘤的形成。然而，尚不知道TLX是否需要用于神经胶质瘤形成。我们使用小鼠模型检查了TLX和几种肿瘤抑制物之间的遗传相互作用，以及TLX依赖性NSC在神经胶质瘤发生过程中的作用。在这里，我们显示了TLX对于成年NSC的增殖必不可少，其中单个缺失 p21 ， p53 或 Pten 或联合缺失 Pten 和 p53 。尽管脑肿瘤仍在 Tlx 突变小鼠中形成，但这些肿瘤的浸润性较小，很少与成年神经源性利基息息相关，提示其非干细胞起源。两者合计，这些结果表明TLX在NSC依赖的神经胶质瘤发生中起关键作用，并暗示TLX作为抑制NSC衍生的脑肿瘤发展的治疗靶标。

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