The role of Wnt signaling in hematopoietic stem cell development.
The role of Wnt signaling in hematopoietic stem cell development.
复制标题
DOI：
10.1080/10409238.2017.1325828
复制
发表时间：
2017-08
影响因子：
6.5
通讯作者：
Willert K
中科院分区：
文献类型：
--
作者：
Richter J;Traver D;Willert K
造血干细胞（HSC）可以自我更新并分化成血液的所有细胞类型。这在治疗上很重要，因为造血干细胞移植可以为血癌和疾病提供疗效。 HSC 的发育过程一直是各种模型生物体中广泛研究的主题，然而，从能够长期多谱系重建的多能前体生产真正的 HSC 的努力还不够。对斑马鱼、鸡和小鼠的研究有助于指导从人类多能干细胞中衍生造血干细胞的努力，并确定了由 FGF、Notch、TGFβ 和 Wnt 等发育调节因子介导的一组复杂的分子信号和细胞相互作用，它们共同促进了向成熟造血干细胞的逐步发育进程。对这些信号的严格时间和空间控制对于生成生物体生命所需的适当数量的 HSC 至关重要。 Wnt 信号蛋白家族在造血发育中的作用已成为许多研究的主题，部分原因是其信号机制的复杂性。通过将细胞命运规范与细胞极性建立相结合，Wnt 能够独特地控制复杂的生物过程，包括胚胎 HSC 发育的多个阶段，从 HSC 规范到从造血上皮出现到随后的扩增。这篇综述重点介绍了特定 Wnt 信号指导和引导斑马鱼和小鼠造血发育的关键信号事件，并将这些发现扩展到当前体外生成 HSC 的工作中。
Hematopoietic stem cells (HSCs) can self renew and differentiate into all cell types of the blood. This is therapeutically important as HSC transplants can provide a curative effect for blood cancers and disorders. The process by which HSCs develop has been the subject of extensive research in a variety of model organisms, however, efforts to produce bona-fide HSC from pluripotent precursors capable of long term multi-lineage reconstitution have fallen short. Studies in zebrafish, chicken and mice have been instrumental in guiding efforts to derive HSCs from human pluripotent stem cells and have identified a complex set of molecular signals and cellular interactions mediated by such developmental regulators as FGF, Notch, TGFβ and Wnt, which collectively promote the stepwise developmental progression towards mature HSCs. Tight temporal and spatial control of these signals is critical to generate the appropriate numbers of HSCs needed for the life of the organism. The role of the Wnt family of signaling proteins in hematopoietic development has been the subject of many studies owing in part to the complex nature of its signaling mechanisms. By integrating cell fate specification with cell polarity establishment, Wnt is uniquely capable of controlling complex biological processes, including at multiple stages of embryonic HSC development, from HSC specification to emergence from the hemogenic epithelium to subsequent expansion. This review highlights key signaling events where specific Wnt signals instruct and guide hematopoietic development in both zebrafish and mice and extends these findings to current efforts of generating HSCs in vitro.
登录
查看更多内容
影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R
影响因子：
2.6
作者：
Kitajima, Kenji;Nakajima, Marino;Hara, Takahiko
通讯作者：
Hara, Takahiko
影响因子：
14.8
作者：
Chen, Baozhi;Dodge, Michael E.;Tang, Wei;Lu, Jianming;Ma, Zhiqiang;Fan, Chih-Wei;Wei, Shuguang;Hao, Wayne;Kilgore, Jessica;Williams, Noelle S.;Roth, Michael G.;Amatruda, James F.;Chen, Chuo;Lum, Lawrence
通讯作者：
Lum, Lawrence
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R