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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

c-Myc抑制剂10074-G5诱导小鼠和人类造血干细胞和祖细胞扩增和HDR调节剂Rad51表达

卷 19, 期 6, 2019

页: [479 - 494] 页: 16

弟呕挨: 10.2174/1568009618666180905100608

价格: $65

摘要

背景:c-Myc在维持糖酵解代谢和造血干细胞(HSC)静止中起主要作用。 目的:靶向HSC静止和代谢调节剂可导致HSC细胞周期进入伴随扩张。 方法和结果:在这里,我们显示c-Myc抑制剂10074-G5处理导致7天后鼠LSKCD34low HSC区室增加2倍。此外,c-Myc抑制增加CD34 +和CD133 +人HSC数量。 c-Myc抑制导致体外和体内糖酵解和细胞周期依赖性激酶抑制剂(CDKI)基因表达的下调。此外,c-Myc抑制上调造血细胞中的主要HDR调节剂Rad51表达。此外,c-Myc抑制不会改变内皮细胞,成纤维细胞或脂肪来源的间充质干细胞的增殖动力学,然而,它限制了骨髓来源的间充质干细胞增殖。我们进一步证明,c-Myc抑制剂10074-G5与牛磺熊去氧胆酸(TUDCA)和i-NOS抑制剂L-NIL的混合物提供了强大的HSC维持和离体扩增,这通过诱导分析的所有干细胞抗原显而易见。有趣的是,c-Myc抑制剂10074-G5,TUDCA和L-NIL的混合物改善了HDR相关基因的表达。 结论:这些发现提供了通过调节HSC糖酵解和HDR途径来改善离体HSC维持和扩增,自体HSC移植和基因编辑的工具。

关键词: 造血干细胞,间充质干细胞,小分子,骨髓,c-myc,同源定向修复。

图形摘要
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