Oct4诱导成年神经干细胞多能性。

Oct4-induced pluripotency in adult neural stem cells.

作者信息

Kim Jeong Beom, Sebastiano Vittorio, Wu Guangming, Araúzo-Bravo Marcos J, Sasse Philipp, Gentile Luca, Ko Kinarm, Ruau David, Ehrich Mathias, van den Boom Dirk, Meyer Johann, Hübner Karin, Bernemann Christof, Ortmeier Claudia, Zenke Martin, Fleischmann Bernd K, Zaehres Holm, Schöler Hans R

机构信息

Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, NRW, Germany.

出版信息

Cell. 2009 Feb 6;136(3):411-9. doi: 10.1016/j.cell.2009.01.023.

DOI:10.1016/j.cell.2009.01.023

PMID:19203577

Abstract

The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem cells (1F iPS) are similar to embryonic stem cells in vitro and in vivo. Not only can these cells can be efficiently differentiated into NSCs, cardiomyocytes, and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.

摘要

四种转录因子Oct4、Sox2、Klf4和c-Myc可诱导小鼠和人成纤维细胞产生多能性。我们之前描述了通过Oct4与Klf4或c-Myc对成年小鼠神经干细胞（NSCs）进行直接重编程。NSCs内源性表达Sox2、c-Myc、Klf4以及几种中间重编程标志物。在此我们报告，生殖系特异性转录因子Oct4的外源性表达足以从成年小鼠NSCs产生多能干细胞。这些单因子诱导多能干细胞（1F iPS）在体外和体内均与胚胎干细胞相似。这些细胞不仅能够在体外高效分化为NSCs、心肌细胞和生殖细胞，而且还能够在体内形成畸胎瘤并进行种系传递。我们的结果表明，Oct4是将NSCs直接重编程为多能性所必需且充分的。