西亚试剂：Nuclear transfer

When Gurdon and Wilmut reprogrammed frog and sheep cells, respectively, they did it by transferring a differentiated nucleus into an egg stripped of its own DNA. Scientists knew that something in the egg was able to reprogram the nucleus, such that the genes associated with being a skin cell, for example, were switched off and those associated with pluripotency were switched on and triggered a cascade of downstream events. In the following decade, researchers found various new ways to reprogram — adding nuclei to fertilized eggs and to embryonic stem cells — but these methods did little to clarify what it was in the cells that did the reprogramming and how the process worked.

That changed when Shinya Yamanaka and Kazutoshi Takahashi at Kyoto University made iPS cells1. They showed that just four proteins that are usually expressed in early embryos or in embryonic stem cells could reprogram an adult cell — and, crucially, they also provided a tool that researchers could use to study reprogramming in a culture dish, something they have been doing ever since. Stem-cell biologists now know that after introducing these proteins — sometimes known as the Yamanaka factors — there is a flurry of intense and mostly predictable gene expression. But then, after a few days, the cells enter a mysterious state in which they are dividing but stalled, failing to reprogram further. After a week or so, a slim few — only one in a thousand — become true pluripotent cells7.

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