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【自选翻译】关于回答维持造血干细胞中Notch 和
翻译如下：
ST：你认为为何你的文章会被高度应用？
干细胞很罕见，因为它们有自我更新的增殖能力。但同时也很难对它进行控制。我认为这篇文章之所以被高度引用是在于我们知道了该如何单独操控这些干细胞以维持它们的生命。尤其是我们知道了Notch signaling是造血干细胞中的强活性物质，并且是其维持未分化状态的关键物质。相反，Wnt signaling主要作用是控制造血干细胞的增殖和残留细胞。这些信息显示Notch signaling主要扮演分裂与定型间一个“选择开关”的作用，并提供Notch 和Wnt在造血干细胞中是如何整合并维持其细胞形态的这样一个模型。
ST：: 它是否是一种新的发现或是有助于其他患者的新方法？
它描述了关于干细胞功能操纵机制的一种新发现。而对自我更新的理解现在停留在分子水平上，仍然不清楚其单独结构是如何进行调整的（即 是分化增殖还是抑制分裂）。我们的研究显示这两个问题是可以被区分的且Notch 和Wnt在干细胞生命的维持中处于附属作用。
St:你能通俗地向大家简要介绍一下它的重要性吗？
因为大多数成熟的造血干细胞的寿命都很有限，造血干细胞使他们自己生存的能力就是不断自我更新和定型自己产生的新细胞以维持生命。我们的研究显示造血干细胞的自我增殖与自我定型之间度的平衡是由 Notch signaling调整的，造血干细胞的生长和生存是由Wnt signaling进行调整的。自从对HSC生长的影响是体外干细胞阔展的关键一步得到验证后,对HSC细胞自我更新规律的了解已有显著的实用性成果，鉴此也可改善白血球过多症和其他癌症的移植效果。
St: 你是如何涉及这项研究的？
我们努力想了解Wnt signaling是怎样影响HSC的.我们发现一些Notch途径的靶标是由Wnt signaling来调节的.这使我们对Notch and Wnt signaling是怎样跟维持干细胞生存的产生兴趣.随着我们对Notch途径怎样影响HSC的了解,我们发现当抑制这个途径的时候会导致细胞的定型.这就预示着Notch signaling活跃在干细胞中且在定型期的时候是无活性或弱活性的.幸运的是我们发现Johns Hopkins已经对Notch进行研究并有报道.于是我们设法跟他合作,这最终也使我们知道了其实在干细胞中Notch signaling是大量存在的,且当干细胞分化后其也迅速关闭.在此状况下我们继续研究,比较Notch 和 Wnt signaling的各自作用,发现 Wnt signaling主要负责细胞的生长和生存, 而Notch signaling则是维持未分化干细胞的基础.
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原文：
ST: Why do you think your paper is highly cited?
Stem cells are unique because they have the ability to balance self-renewal with commitment; however, the signals that control this are not fully understood. I think this paper is highly cited because we show how distinct signals interact to control stem cell maintenance. Specifically we show that Notch signaling is highly active in hematopoietic stem cells (HSCs), and is critical for maintaining their undifferentiated state. In contrast, Wnt signaling appears to predominantly control proliferation and survival of HSCs. These data suggest that Notch signaling acts as a switch between renewal and commitment, and provide a model for how Notch and Wnt may be integrated by HSCs to maintain the stem cell state.
SToes it describe a new discovery or a new methodology that's useful to others?
This work describes a discovery about the mechanisms that control stem cell function. While self-renewal is now beginning to be understood at a molecular level, what remains unclear is how its individual elements (i.e., proliferation and inhibition of differentiation) are regulated. Our work suggests that these two events can be uncoupled and that Notch and Wnt play complementary roles in stem cell maintenance.
ST:Could you summarize the significance of your paper in layman's terms?
Because most mature blood stem cells have a limited lifespan, the ability of HSCs to perpetuate themselves through self-renewal and generate new blood cells through commitment is critical to sustaining life. Our work shows that the balance between HSC self-renewal and commitment is regulated by Notch signaling, and that HSC growth and survival are regulated by Wnt signaling. Progress in the basic understanding of regulation of HSC self-renewal has significant practical ramifications, since identification of factors that influence HSC growth is a critical step towards defining ways to expand stem cells in vitro, thereby improving transplantation-based therapies for leukemias and other cancers
ST:How did you become involved in this research?
In our effort to understand how Wnt signaling exerts its influence on HSCs, we discovered that some transcriptional targets of the Notch pathway were upregulated by Wnt signaling. This got us interested in understanding how Notch and Wnt signaling may be linked in the context of stem cell maintenance. As we followed the Notch pathway to determine how it influenced HSCs, we found that inhibiting the pathway led to increased commitment. This made a prediction that Notch signaling should be active in stem cells and mostly inactive during commitment. Fortunately around this time, we found out that Nick Gaiano at Johns Hopkins had generated a Notch reporter mouse. We set up in collaboration with him and this allowed us to show that Notch signaling was in fact highly enriched in stem cells, and was rapidly shut off as stem cells differentiated. We then went on to define the relative roles of Notch and Wnt signaling in this context and found that Wnt signaling was dominant in influencing growth and survival, and Notch signaling was essential for maintaining the undifferentiated state.
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作者:admin@医学,生命科学 2011-03-04 05:14
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