Scientists generate type of human stem cell that is ‘easier to edit’

Because they have just a single copy of a gene to target, haploid human cells may constitute a powerful tool for genetic screens.

By JUDY SIEGEL-ITZKOVICH
DNA structure [Illustrative] (photo credit: INIMAGE)
DNA structure [Illustrative]
(photo credit: INIMAGE)
Medical researchers are limited in their work by the fact that human cells are “diploid,” meaning they contain two copies of the human genome. This makes it difficult to detect the effects of genetic mutations, because for each diseased gene, there is a second, normal copy as “backup.”
But now, Hebrew University of Jerusalem and Columbia University of New York scientists have generated a type of human stem cell that has half a genome. The stem cells are the first known human cells capable of cell division with just one copy of the parent cell’s genome (one set of 23 chromosomes, rather than the usual 23 chromosomes from the mother and 23 from the father). They may yield genetic screening tools and therapies, the scientists said.
These new human stem cells will have a “profound impact on human genetic and medical research,” according to HU Prof. Nissim Benvenisty, director of the Azrieli Center for Stem Cells and Genetic Research and principal co-author of the study.
“One of the greatest advantages of using haploid human cells is that it is much easier to edit their genes,” said Ido Sagi, the doctoral student who led the research.
The US team was led by developmental cell biologist Prof. Dieter Egli of Columbia University Medical Center and the New York Stem Cell Foundation Research Institute.
Because they have just a single copy of a gene to target, haploid human cells may constitute a powerful tool for genetic screens.
“Being able to affect single-copy genes in haploid human stem cells has the potential to facilitate genetic analysis in biomedical fields such as cancer research, precision and regenerative medicine,” they said. Since the stem cells described in the study were a genetic match to the egg cell donor, they could be used to develop cellbased therapies for diseases such as blindness, diabetes, or other conditions in which genetically identical cells offer a therapeutic advantage.
And because their genetic content is equivalent to germ cells, these cells will provide researchers with a novel tool for understanding human development and the reasons why we reproduce sexually, instead of from a single parent, and could have implications for human reproductive therapies.
The scientists said that these were the first human cells known to be capable of cell division with just one copy of the parent cell’s genome. The cells are pluripotent – meaning that they can turn into many other cell types, including nerve, heart and pancreatic cells – while retaining a single set of chromosomes.
Previous efforts to generate embryonic stem cells using human egg cells had resulted in diploid stem cells. In this study, the scientists triggered unfertilized human egg cells into dividing. They then highlighted the DNA with a fluorescent dye and isolated the haploid stem cells, which were scattered among the more populous diploid cells.
“This work is an outstanding example of how collaborations between different institutions, on different continents, can solve fundamental problems in biomedicine,” said Egli.
THE NECKLACE THAT HEARS WHAT YOU EAT Carrots and apples not only taste different; they also make distinct sounds when chewed. This is not a trivial fact but very important in the University at Buffalo lab of computer science Prof. Wenyao Xu, who is creating a library that catalogues the unique sounds that foods make as we bite, grind and swallow them. The library is part of a software package that supports AutoDietary, a hi-tech, food-tracking necklace being developed by Xu and researchers at Northeastern University in China.
Described in a study published February by IEEE Sensors Journal, AutoDietary is like Fitbit and other wearable devices that track burned calories. It monitors caloric intake – in other words, what we eat – at the neck.
“There is no shortage of wearable devices that tell us how many calories we burn, but creating a device that reliably measures caloric intake isn’t so easy,” said Xu. AutoDietary wraps around the back of the neck like a choker necklace. A tiny high-fidelity microphone – about the size of a zipper pull – records the sounds made during mastication and as the food is swallowed.
That data is sent to a smartphone via Bluetooth, where food types are recognized.
The study describes how 12 test subjects, male and female, aged 13 to 49, were given water and six types of food – apples, carrots, potato chips, cookies, peanuts and walnuts. AutoDietary was able to accurately identify the correct food and drink 85 percent of the time.
“Each food, as it’s chewed, has its own voice,” said Xu, who noted that the device could someday help people suffering from diabetes, obesity, bowel disorders and other ailments by enabling them to better monitor their food intake and thus improve how they manage their conditions. Xu plans future studies to build upon his library by testing different foods and recording the sounds they make. He also intends to refine the algorithms used to differentiate the foods to improve AutoDietary’s ability to recognize what’s being eaten.
While promising, a wearable necklace that measures sound has limitations when used alone. For example, it cannot differentiate between similar foods such as frosted corn flakes and regular corn flakes or distinguish the ingredients of complex foods such as soup or chili.
To address these limitations, Xu is planning a biomonitoring device that would complement AutoDietary by being activated once the necklace recognizes that the user is eating a general category of food.
The biomonitor would then determine the nutritional value of the food via blood sugar levels and other measurements.
The system would then gather and present this information on a smartphone, while providing suggestions on healthier eating.
The beauty of the system, Xu says, is that the user isn’t overwhelmed by a continuous stream of information, as the system is active only during eating.