Kalani M Yashar S, Cheshier Samuel H, Cord Branden J, Bababeygy Simon R, Vogel Hannes, Weissman Irving L, Palmer Theo D, Nusse Roel
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16970-5. doi: 10.1073/pnas.0808616105. Epub 2008 Oct 28.
In this work we have uncovered a role for Wnt signaling as an important regulator of stem cell self-renewal in the developing brain. We identified Wnt-responsive cells in the subventricular zone of the developing E14.5 mouse brain. Responding cell populations were enriched for self-renewing stem cells in primary culture, suggesting that Wnt signaling is a hallmark of self-renewing activity in vivo. We also tested whether Wnt signals directly influence neural stem cells. Using inhibitors of the Wnt pathway, we found that Wnt signaling is required for the efficient cloning and expansion of single-cell derived populations that are able to generate new stem cells as well as neurons, astrocytes, and oligodendrocytes. The addition of exogenous Wnt3a protein enhances clonal outgrowth, demonstrating not only a critical role for the Wnt pathway for the regulation of neurogenesis but also its use for the expansion of neural stem cells in cell culture and in tissue engineering.
在这项研究中，我们发现Wnt信号通路在发育中的大脑中作为干细胞自我更新的重要调节因子发挥作用。我们在发育中的E14.5小鼠脑室下区鉴定出Wnt反应性细胞。在原代培养中，反应性细胞群体富含自我更新的干细胞，这表明Wnt信号通路是体内自我更新活动的一个标志。我们还测试了Wnt信号是否直接影响神经干细胞。使用Wnt通路抑制剂，我们发现Wnt信号通路对于能够产生新的干细胞以及神经元、星形胶质细胞和少突胶质细胞的单细胞衍生群体的有效克隆和扩增是必需的。添加外源性Wnt3a蛋白可增强克隆生长，这不仅证明了Wnt通路在神经发生调节中的关键作用，也证明了其在细胞培养和组织工程中用于扩增神经干细胞的用途。
