Understanding molecular mechanisms in human ES/iPS cell renewal and development of defined culture system

迄今为止，调节人ES/iPS细胞自我更新的外在因素还不完全清楚，但bFGF和TGF β信号传导形成了大多数人ES/iPS细胞增殖系统的基石。在以前的研究中，我们已经确定了一种DYRK抑制剂，可以调节Wnt通路，支持Wnt诱导的自我更新，而不诱导分化。利用Wnt和化合物，我们已经开发了一种定义的无异种培养系统，该系统允许在没有FGF/TGF β补充的情况下长期扩增人ES/iPS细胞。在进一步的研究中，我们已经确定了参与DYRK抑制/Wnt依赖性自我更新的几个关键途径，并发现小化合物可以控制这些途径。利用这些化合物，我们已经开发了一种新的和简单的人ES/iPS细胞的确定性培养系统。

The extrinsic factors regulating human ES/iPS cell self-renewal are incompletely understood to date, but bFGF and TGFß signaling form the cornerstone of most systems for human ES/iPS cell propagation. In previous study, we have identified a DYRK inhibitor that could modulate Wnt pathway and support Wnt-induced self-renewal without inducing differentiation. Utilizing Wnt and the compound, we have developed a defined xeno-free culture system that allows for long-term expansion of human ES/iPS cells without FGF/TGFß supplementation. In further investigation, we have identified several key pathways involved in DYRK inhibition/Wnt-dependent self-renewal and found small chemical compounds can control these. Utilizing these chemical compounds, we have developed a novel and simple defined-culture system for human ES/iPS cells.