Identification of KLF9 and BCL3 as transcription factors that enhance reprogramming of primordial germ cells.
Identification of KLF9 and BCL3 as transcription factors that enhance reprogramming of primordial germ cells.
复制标题
DOI：
10.1371/journal.pone.0205004
复制
发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Matsui Y
中科院分区：
文献类型：
--
作者：
Otsuka K;Takehara A;Chiba N;Matsui Y
原始生殖细胞（PGCs）是卵子和精子的前体。虽然PGCs在体内是单能细胞，但在体外白血病抑制因子和碱性成纤维细胞生长因子（bFGF）存在下，它们被重编程为多能干细胞（PSC），也称为胚胎生殖细胞（EGCs）。然而，负责其重编程的分子机制尚未完全了解。在这里，我们展示了介导PGC重编程的转录因子的鉴定。我们通过计算机分析和RT-qPCR选择了在PGCs和PSC之间表达显著不同的转录因子或表观遗传调控因子的编码基因。在候选基因中，Bcl 3或Klf 9的过表达（OE）显著增强PGC重编程。值得注意的是，即使没有bFGF，Klf 9-OE也刺激EGC形成。参与PGC重编程的G蛋白偶联受体信号传导相关通路在Klf 9-OE下调的基因中富集，并且激活腺苷酸环化酶的毛喉素通过敲低Klf 9来拯救被抑制的EGC形成，这表明KLF 9与这种信号传导之间存在分子联系。
Primordial germ cells (PGCs) are precursors of eggs and sperm. Although PGCs are unipotent cells in vivo, they are reprogrammed into pluripotent stem cells (PSCs), also known as embryonic germ cells (EGCs), in the presence of leukemia inhibitory factor and basic fibroblast growth factor (bFGF) in vitro. However, the molecular mechanisms responsible for their reprogramming are not fully understood. Here we show identification of transcription factors that mediate PGC reprogramming. We selected genes encoding transcription factors or epigenetic regulatory factors whose expression was significantly different between PGCs and PSCs with in silico analysis and RT-qPCR. Among the candidate genes, over-expression (OE) of Bcl3 or Klf9 significantly enhanced PGC reprogramming. Notably, EGC formation was stimulated by Klf9-OE even without bFGF. G-protein-coupled receptor signaling-related pathways, which are involved in PGC reprogramming, were enriched among genes down-regulated by Klf9-OE, and forskolin which activate adenylate cyclase, rescued repressed EGC formation by knock-down of Klf9, suggesting a molecular linkage between KLF9 and such signaling.
登录
查看更多内容
影响因子：
64.8
作者：
MATSUI, Y;TOKSOZ, D;HOGAN, BLM
通讯作者：
HOGAN, BLM
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
5.3
作者：
NOLAN, GP;FUJITA, T;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Tanabe, Koji;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
影响因子：
4.6
作者：
Kimura, Tohru;Tomooka, Maya;Nakano, Toru
通讯作者：
Nakano, Toru