Discovery Suggests a New Avenue for Advancing Stem Cell Research

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By Veronique Greenwood
Oct 7, 2011 8:13 PMNov 20, 2019 1:53 AM

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What's the News: Making stem cells without using embryos can be a difficult process, and scientists have had to cope with numerous failures. But a new discovery may help them home in on what's missing from their biochemical recipes. What's the Context:

  • Induced pluripotent stem cells (iPSs) are cells that have had their biological clocks turned back to the point where they can develop into anything---blood cells, liver cells, you name it. Scientists hope to eventually work this magic on skin or blood cells removed from a patient desperately in need of new pancreatic cells, for instance, into order to grow them replacements.

  • The primary method for making iPSs involves inserting four genes into the cells you'd like to reprogram. The proteins those genes code for are usually found in embryonic stem cells, and they direct the cell to reset itself and begin to divide.

  • But cells made this way can have a lot of mistakes in their genetic code, which can turn them into tumor cells, and it appears that that their memory of their early identities aren't always fully erased. (Check out Ed Yong's interactive timeline of stem cell history for more.)

How the Heck:

  • To address this problem, this team of scientists went back to stem cells' roots: they worked on swapping out the nucleus of a donated human egg and replacing it with a nucleus from a patient's cell, an approach that had been used in the early days of studying stem cells. The idea is that unknown substances in the egg can reset the nucleus, and then as the egg-patient cell hybrid grows and divides, scientists can skim off the reprogrammed cells, which, courtesy of their nucleus, are compatible with the patient, and use them in treatments.

  • The way it's usually done, though, the hybrid cell almost never makes it that far---it fails to divide enough to make it to the point where cells can be skimmed off. But when the team accidentally left the egg's nucleus in the cell along with the new nucleus, they found that the cells made it to that point far more frequently than they had without the egg's nucleus.

  • While cells made this way aren't suitable for use in patients---for one thing, they have an extra set of chromosomes, thanks to the egg nucleus---this suggests that there is something that the egg nucleus itself is producing to keep the cells viable.

The Future Holds: The discovery that the egg nucleus can keep the hybrid cells growing is in and of itself not such a shocker: The nucleus, of course, carries the genes that code for the proteins that make eggs viable. But knowing definitively that an egg nucleus can coax these hybrid cells into dividing will help scientists narrow the field of candidates. Hopefully they will be able to find several more proteins they can add when making iPSs the usual way, in addition to the four they already use. Reference: Noggle, S. et al. Human oocytes reprogram somatic cells to a pluripotent state.

Nature 478, 70–75 (2011)

Image courtesy of PLoS

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