西亚试剂：A class of its own

The headline finding is the new category of pluripotent cell, called F-class cells after the fuzzy appearance of the cell colonies. These cells were produced with a small tweak to the iPS-cell recipe: instead of stopping expression of the reprogramming factors after a few days, the researchers continued to supply them. “That leads to a bifurcation,” says Nagy.

F-class cells are different from iPS cells because they fail one of the most stringent tests of pluripotency: when injected into mouse embryos they cannot contribute to tissues in the resulting chimaeric mice. For this reason, some critics say that F-class cells could be what other scientists have been calling 'partially reprogrammed' cells. But Nagy says that cells do not have to contribute to chimaeras to be considered pluripotent, and points to the cells' other characteristics of pluripotency: for example, they form what is known as a teratoma, which contains a range of differentiated cell types.

Nagy says that others have overlooked the F-class state because they were only looking for cells that were similar to embryonic stem cells, whereas his team was “unbiased by expectation of what pluripotency should look like”. He thinks that there are more states of pluripotency to be found, and his group will be looking for them in its hard drives. “It's a conceptually important thing, it opens up a big door,” he says.

All these studies are adding fuel to a central debate in the reprogramming community: does the process have an inherently random and unpredictable element to it? Until recently, there was a general consensus that this was true. According to this 'stochastic' model, as the reprogramming factors trigger cascades of molecules, some cells will drift into a reprogrammed state and some will not, and which way they go cannot be predicted.

But some studies, including one by Hanna12 show that the reprogramming method can be tweaked to make the process more efficient — suggesting that the randomness can be controlled or even eliminated. These studies imply that reprogramming can be switched from a stochastic process to a deterministic one, in which one step inevitably follows the next to a new cell state.

Many scientists now say that reprogramming involves both deterministic phases — at the start and end — and a stochastic phase, which is the mysterious week in the middle. Hanna plays down the debate altogether, seeing little contradiction between the two sides. “I do not believe there is a stochastic versus deterministic camp.” He compares reprogramming to flipping a coin: each flip will have a random outcome, but after 100 flips, close to 50% of them will have come up heads. Similarly, whether a given cell flips into a reprogrammed state might be random. But over time, a reprogramming method should produce a certain percentage — maybe 10% — of pluripotent cells every time. Further experiments might resolve the debate, says Zaret, by pinpointing the events that snap the cells out of their week-long lethargy.

For Zaret, the reprogramming debate offers a window on a bigger concept: how order in biology arises from randomness. “Cellular systems are built upon intrinsic noise and stochastic events that somehow elicit cell fates that are locked down and do not switch back and forth,” he says. This question is at the basis of cell type control, he says, and draws him to the research.

For others, like Yamanaka, the incentive to open the black box is a practical one. More-efficient reprogramming makes for better experiments and a more reliable source of cells that can eventually be used in human medicine. “The motivation of my research is to treat patients,” he says. “Anything that helps push iPS cells into the clinic excites me.”

以上资料由西亚试剂：http://www.xiyashiji.com/ 提供