Scientists have already found their way to transform human cells into new shapes, using a special mixture of chemicals to nudge humble skin cells into resilient tissues known as induced pluripotent stem cells.
Despite this new lease on life, these specific cells still retain some genetic reminders of their time as mature tissue, which affects their use as a blank slate.
Now an international team of researchers has done an even better job: finding a new way to clear a cell’s memory so it can be better reprogrammed as a stem cell.
This may all sound like some molecular magic, however Includes pluripotent stem cells iPSCs, as they are known, have been used in medical research to model diseases and develop treatments since 2006.
Their discovery, made by two Japanese scientists, opened up a new realm of regenerative medicine, as embryonic stem cells can be engineered from normal adult human cells using a range of reprogramming factors.
the The promise of iPSCs is enormousBecause they can spread endlessly and give rise to every other cell type in the body, iPSCs are not only incredibly useful tools for studying diseases. It also serves as a stepping stone towards individuality Cell-based therapiesWhich can replace damaged or diseased tissue.
In the lab, scientists have used iPS cells to grow heart tissue that beats like real heart cells and engineer mini replicas of organs, called organelles.
But the process of forming iPSCs is not perfect: some cells retain epigenetic modifications applied to their DNA in their differentiated state, or even undergo spontaneous changes to these epigenetic “memories” that can influence cell behaviour.
“This could create functional differences between pluripotent stem cells and the embryonic stem cells they are supposed to mimic, and the specialized cells later derived from them, limiting their use.” Explain Study author Ryan Lister, a genomic biologist at the University of Western Australia.
So Lister and his colleagues sought to understand when these abnormalities appear during cell reprogramming and how to avoid or erase them and other lingering signs.
The team profiled gene expression as the cells moved through the reprogramming process, to see which genes were turned on and when.
A large portion of the cell’s DNA is coiled Large proteins called histonesprotecting those parts of the cellular machinery whose job it is to decode genes into proteins.
Depending on where the histones are located, the cell may not respond to chemical signals sent to it by scientists, in which case it carries an epigenetic memory through the reprogramming process.
The new method, called transient naïve (TNT) reprogramming, mimics the cell genome resetting of a cell that occurs in very early embryonic development, both before and after implantation of the same embryo into the uterine wall.
In a series of experiments on cells, the researchers show up TNT reprogramming “effectively erases epigenetic memory,” especially in highly populated DNA regions — but without deleting other important information. imprinted on the genome.
As a result, the reprogrammed cells better resemble embryonic stem cells in function and at the molecular level.
“We expect that TNT reprogramming will establish a new standard for cell therapies and biomedical research, and will greatly advance their progress.” He says Leicester.
“It solves the problems associated with conventionally generated induced pluripotent stem cells which if unaddressed can have very detrimental consequences for long-term cell therapies.” Add Jia Tan, study author and cell biologist at Monash University in Melbourne.
The study was published in nature.
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