Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
Differentiation. 2010 Jul;80(1):9-19. doi: 10.1016/j.diff.2010.05.001. Epub 2010 May 27.
While endogenous Myc (c-myc) and Mycn (N-myc) have been reported to be separately dispensable for murine embryonic stem cell (mESC) function, myc greatly enhances induced pluripotent stem (iPS) cell formation and overexpressed c-myc confers LIF-independence upon mESC. To address the role of myc genes in ESC and in pluripotency generally, we conditionally knocked out both c- and N-myc using myc doubly homozygously floxed mESC lines (cDKO). Both lines of myc cDKO mESC exhibited severely disrupted self-renewal, pluripotency, and survival along with enhanced differentiation. Chimeric embryos injected with DKO mESC most often completely failed to develop or in rare cases survived but with severe defects. The essential nature of myc for self-renewal and pluripotency is at least in part mediated through orchestrating pluripotency-related cell cycle and metabolic programs. This study demonstrates that endogenous myc genes are essential for mESC pluripotency and self-renewal as well as providing the first evidence that myc genes are required for early embryogenesis, suggesting potential mechanisms of myc contribution to iPS cell formation.
虽然内源性 Myc（c-myc）和 Mycn（N-myc）已被报道分别可用于维持小鼠胚胎干细胞（mESC）的功能，但 myc 极大地增强了诱导多能干细胞（iPS）的形成，而过表达的 c-myc 赋予 mESC 对 LIF 的独立性。为了研究 myc 基因在 ESC 中和普遍的多能性中的作用，我们使用 myc 双纯合 floxed mESC 系（cDKO）条件性敲除了 c-和 N-myc。两条 myc cDKO mESC 系均表现出严重的自我更新、多能性和存活受损，同时伴有增强的分化。用 DKO mESC 注射的嵌合胚胎通常完全不能发育，或者在极少数情况下存活，但存在严重缺陷。Myc 对于自我更新和多能性的必需性至少部分是通过协调多能性相关的细胞周期和代谢程序来介导的。这项研究表明，内源性 myc 基因对于 mESC 的多能性和自我更新是必需的，并且首次提供了证据表明 myc 基因对于早期胚胎发生是必需的，这表明了 myc 基因在 iPS 细胞形成中的潜在作用机制。
