The Pleiotropic Effects of the Canonical Wnt Pathway in Early Development and Pluripotency.
The Pleiotropic Effects of the Canonical Wnt Pathway in Early Development and Pluripotency.
复制标题
DOI：
10.3390/genes9020093
复制
发表时间：
2018-02-14
期刊：
影响因子：
3.5
通讯作者：
Lluis F
中科院分区：
文献类型：
--
作者：
de Jaime-Soguero A;Abreu de Oliveira WA;Lluis F
分别从早期胚胎阶段和成体体细胞中获得胚胎干细胞和诱导多能干细胞的技术，成为建立新的体外模型的强大资源，这些模型重现了早期发育过程和疾病。此外，多能干细胞（PSC）代表了相关分化细胞类型的宝贵来源，具有再生医学和细胞替代疗法的巨大潜力。多能干细胞支持自我更新，效力和体外培养的广泛时期的增殖。然而，直到最近才开始澄清这些PSC特有的细胞特征中的每一个的核心途径。Wnt信号通路在早期胚胎发生过程中是关键的，并且对于PSC的多能性的诱导和维持是中心的。Wnt家族配体的信号传导通过β-连环蛋白在细胞质和细胞核中的稳定化在细胞内传递，在细胞核中，它增强T细胞因子（TCF）/淋巴增强因子（LEF）家族转录因子的转录活性。有趣的是，在PSC中，Wnt/β-catenin-TCF/LEF轴具有几种不相关且有时相反的细胞功能，例如自我更新、干细胞性、谱系定型和细胞周期调节。此外，Wnt信号传导途径的严格控制增强了体细胞的重编程以诱导多能性。最近的几项研究工作强调了Wnt信号通路在多能状态下的多效性功能。尽管如此，相互矛盾的结果和悬而未决的问题仍然存在。在这篇综述中，我们将重点介绍经典Wnt信号通路在胚胎着床前发育过程中的不同功能，以及它在多能干细胞生物学中的作用，如自我更新和细胞周期调控以及体细胞重编程。
The technology to derive embryonic and induced pluripotent stem cells from early embryonic stages and adult somatic cells, respectively, emerged as a powerful resource to enable the establishment of new in vitro models, which recapitulate early developmental processes and disease. Additionally, pluripotent stem cells (PSCs) represent an invaluable source of relevant differentiated cell types with immense potential for regenerative medicine and cell replacement therapies. Pluripotent stem cells support self-renewal, potency and proliferation for extensive periods of culture in vitro. However, the core pathways that rule each of these cellular features specific to PSCs only recently began to be clarified. The Wnt signaling pathway is pivotal during early embryogenesis and is central for the induction and maintenance of the pluripotency of PSCs. Signaling by the Wnt family of ligands is conveyed intracellularly by the stabilization of β-catenin in the cytoplasm and in the nucleus, where it elicits the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of transcription factors. Interestingly, in PSCs, the Wnt/β-catenin–TCF/LEF axis has several unrelated and sometimes opposite cellular functions such as self-renewal, stemness, lineage commitment and cell cycle regulation. In addition, tight control of the Wnt signaling pathway enhances reprogramming of somatic cells to induced pluripotency. Several recent research efforts emphasize the pleiotropic functions of the Wnt signaling pathway in the pluripotent state. Nonetheless, conflicting results and unanswered questions still linger. In this review, we will focus on the diverse functions of the canonical Wnt signaling pathway on the developmental processes preceding embryo implantation, as well as on its roles in pluripotent stem cell biology such as self-renewal and cell cycle regulation and somatic cell reprogramming.
登录
查看更多内容
影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
10.5
作者：
Cole, Megan F.;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
11.8
作者：
Doble, Bradley W.;Patel, Satish;Woodgett, James R.
通讯作者：
Woodgett, James R.
影响因子：
7.2
作者：
Cadigan, Ken M.;Waterman, Marian L.
通讯作者：
Waterman, Marian L.