Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
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DOI：
10.1038/nbt.1502
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发表时间：
2008-11-01
影响因子：
46.9
通讯作者：
Melton, Douglas A.
中科院分区：
文献类型：
--
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
特定遗传因子的异位表达可以将体细胞重编程为与胚胎干细胞非常相似的诱导多能干细胞（iPS）。iPS细胞衍生的低效率阻碍了对重编程的分子机制的研究，并且病毒转基因，特别是癌基因c-Myc和Klf 4的整合可能阻碍该方法用于人类治疗应用。在这里，我们报告，丙戊酸（VPA），组蛋白去乙酰化酶抑制剂，使原代人成纤维细胞的重编程只有两个因素，Oct 4和Sox 2，而不需要癌基因c-Myc或Klf 4。这两种因子诱导的人iPS细胞在多能性、全局基因表达谱和表观遗传状态方面类似于人ES细胞。这些结果支持了通过纯化学手段重编程的可能性，这将使重编程细胞的治疗用途更安全和更实用。
Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical.