Scientists have managed to convert mouse skin cells directly into motor neurons, skipping the usual step of stem cells in between. Depositphotos –
Cooking up a batch of stem cells to treat illness or injury used to involve the ethically hairy practice of harvesting them from embryonic tissue. But in 2006, Japanese scientists identified a way to revert mature cells back into stem cells. From there, these induced pluripotent stem cells (iPSCs) can be coaxed to become whatever cell type is needed for a specific treatment.
However, this Nobel prize-winning discovery isn’t without its own problems. For one, a large portion of the cells can get stuck in the intermediate stages, reducing the efficiency of the technique. In the original study less than 0.1% of cells made it all the way through, although that’s been drastically improved in the almost 20 years since, with some methods closing in on 100%.
Now, scientists at MIT have found a way to cut out the middle man, bypassing the stem cell step and going straight from one cell type to another. Better yet, it boasts an incredible efficiency of over 1,000%. In other words, for every one source cell, you’re getting 10 or more target cells.
“Oftentimes, one of the challenges in reprogramming is that cells can get stuck in intermediate states,” said Katie Galloway, senior author of two papers describing the new technique. “So, we’re using direct conversion, where instead of going through an iPSC intermediate, we’re going directly from a somatic cell to a motor neuron.”
The original process involved a set of four genes that code for proteins called transcription factors. Packaging these into virus vectors and delivering them to the skin cells converted them into iPSCs.
For the new study, the researchers experimented with six transcription factors from previous work, trying different combinations to find the fewest that could still be effective. After much trial and error, they identified a combo of three, known as NGN2, ISL1 and LHX3, which could perform the conversion.
Just using these three allowed all of them to be crammed into one viral vector, allowing for the right dosage to reach every cell. Using a second virus, the team delivered two other genes that cause the cells to start proliferating first.
“If you were to express the transcription factors at really high levels in nonproliferative cells, the reprogramming rates would be really low, but hyperproliferative cells are more receptive,” said Galloway. “It’s like they’ve been potentiated for conversion, and then they become much more receptive to the levels of the transcription factors.”
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Both studies were published in the journal Cell Systems. Source: MIT
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