There are many unknown elements for what triggers the cells in an embryo to start dividing and multiplying and becoming every single cell in the body. Now researchers at the Gladstone Institutes in San Francisco have uncovered one of those elements, how embryos determine which cells become the head and which the tail.
In this CIRM-funded study the Gladstone team, led by Dr. Todd McDevitt, discovered almost by chance how the cells align in a heads-to-tail arrangement.
They had created an organoid made from brain cells when they noticed that some of the cells were beginning to gather in an elongated fashion, in the same way that spinal cords do in a developing fetus.
In a news article, Nick Elder, a graduate student at Gladstone and the co-author of the study, published in the journal Development, says this was not what they had anticipated would happen: “Organoids don’t typically have head-tail directionality, and we didn’t originally set out to create an elongating organoid, so the fact that we saw this at all was very surprising.”
Further study enabled the team to identify which molecules were involved in signaling specific genes to switch on and off. These were similar to the process previously identified in developing mouse embryos.
“This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,” says McDevitt.
This is not just of academic interest either, it could have real world implications in helping understand what causes miscarriages or birth defects.
“We can use this organoid to get at unresolved human developmental questions in a way that doesn’t involve human embryos,” says Dr. Ashley Libby, another member of the team. “For instance, you could add chemicals or toxins that a pregnant woman might be exposed to, and see how they affect the development of the spinal cord.”
Last week’s news headlines were dominated by one big story, the use of a stem cell transplant to effectively cure a person of HIV. But there were other stories that, while not quite as striking, did also highlight how the field is advancing.
A new way to boost brain cells
It’s hard to fix
something if you don’t really know what’s wrong in the first place. It would be
like trying to determine why a car is not working just by looking at the hood
and not looking inside at the engine. The human brain is far more complex than
a car so trying to determine what’s going wrong is infinitely more challenging.
But a new study could help give us a new option.
Luxembourg and Germany have developed a new computer model for what’s happening
inside the brain, identifying what cells are not operating properly, and fixing
Antonio del Sol, one
of the lead authors of the study – published in the journal Cell
– says their new model allows them to identify which stem cells are active and
ready to divide, or dormant.
“Our results constitute an important
step towards the implementation of stem cell-based therapies, for instance for
neurodegenerative diseases. We were able to show that, with computational
models, it is possible to identify the essential features that are
characteristic of a specific state of stem cells.”
The work, done in
mice, identified a protein that helped keep brain stem cells inactive in older
animals. By blocking this protein they were able to help “wake up” those stem
cells so they could divide and proliferate and help regenerate the aging brain.
And if it works in
mice it must work in people right? Well, that’s what they hope to see next.
Deeper understanding of fetal development
According to the Mayo
Clinic between 10 and 20 percent of known pregnancies end in
miscarriage (though they admit the real number may be even higher) and our lack
of understanding of fetal development makes it hard to understand why. A new
study reveals a previously unknown step in this development that could help
provide some answers and, hopefully, lead to ways to prevent miscarriages.
Researchers at the
Karolinska Institute in Sweden used genetic sequencing to follow the
development stages of mice embryos. By sorting those different sequences into a
kind of blueprint for what’s happening at every stage of development they were
able to identify a previously unknown phase. It’s the time between when the
embryo attaches to the uterus and when it begins to turn these embryonic stem
cells into identifiable parts of the body.
Lead researcher Qiaolin Deng says this finding provides vital new evidence.
“Being able to follow the
differentiation process of every cell is the Holy Grail of developmental
biology. Knowledge of the events and factors that govern the development of the
early embryo is indispensable for understanding miscarriages and congenital
disease. Around three in every 100 babies are born with fetal malformation
caused by faulty cellular differentiation.”
Could a new drug discovery
reduce damage from a heart attack?
Every 40 seconds someone in the US has a heart attack. For many it is fatal but even for those who survive it can lead to long-term damage to the heart that ultimately leads to heart failure. Now British researchers think they may have found a way to reduce that likelihood.
Using stem cells to
create human heart muscle tissue in the lab, they identified a protein that is
activated after a heart attack or when exposed to stress chemicals. They then
identified a drug that can block that protein and, when tested in mice that had
experienced a heart attack, they found it could reduce damage to the heart
muscle by around 60 percent.
Prof Michael Schneider,
the lead researcher on the study, published in Cell
Stem Cell, said this could be a game changer.
“There are no
existing therapies that directly address the problem of muscle cell death and
this would be a revolution in the treatment of heart attacks. One reason why
many heart drugs have failed in clinical trials may be that they have not been
tested in human cells before the clinic. Using both human cells and animals
allows us to be more confident about the molecules we take forward.”
As reported in the journal PLOS Genetics, UNC researchers identified a gene that does not obey traditional laws that determine how genes get passed down from parents to offspring. In experiments on laboratory mice, they found a gene called R2d2 causes female mice to pass on more genetic information than the males did—an observation that appears to contradict principles of genetic inheritance set forth more than a century ago.
As you may (or may not) remember from freshmen biology class, the laws of inheritance were laid down by the 19th century monk Gregor Mendel. Through meticulous observations of his garden’s pea plants, he found that each parent contributes their genetic information equally to their offspring.
But 150 years of scientific discovery later, scientists have discovered that this isn’t always the case.
Instead, in some cases one of the parents will contribute a greater percentage of genetic information than the other, a process called meiotic drive. Scientists had seen evidence of this process occurring in mammals for quite some time, but hadn’t narrowed down the driver of the process to a particular gene. According to UNC researchers, R2d2 is that gene. Senior author Fernando Pardo-Manuel de Villena explains:
“R2d2 is a good example of a poorly understood phenomenon known as female meiotic drive—when an egg is produced and a ‘selfish gene’ is segregated to the egg more than half the time.”
Pardo-Manuel de Villena notes that one example of this process occurs during trisomies—when three chromosomes (two from one parent and one from the other) are passed down to the embryo. The most common trisomy, trisomy 21, is more commonly known as Down Syndrome.
With these findings, Pardo-Manuel de Villena and the team are hoping to gain important insights into the underlying cause of trisomies, as well as the underlying causes for miscarriage—which are often not known.
“Understanding how meiotic drive works may shed light on the … abnormalities underlying these disorders,” said Pardo-Manuel de Villena.
This research was performed in large part by first author John Didion, who first discovered R2d2 when breeding two different types of mice for genetic analysis. Using whole-genome sequencing of thousands of laboratory mice, Didion and his colleagues saw that genes were passed down equally from each mouse’s parents. But a small section, smack dab in the middle of chromosome 2, was different.
Further analysis revealed that this section of chromosome 2 had a disproportionately larger number of genes from the mouse’s mother, compared to its father—showing a clear example of female meiotic drive. And at the heart of it all, Didion discovered, was the R2d2 gene.
The UNC team are already busy diving deeper into the relationship between R2d2 and meiotic drive with a focus on understanding, and one day perhaps correcting, genetic abnormalities in the developing embryo.