Building a Blueprint for the Human Brain

How does a brain blossom from a small cluster of cells into nature’s most powerful supercomputer? The answer has long puzzled scientists, but with new advances in stem cell biology, researchers are quickly mapping the complex suite of connections that together make up the brain.

UCLA scientists have developed a new system that can map the development of brain cells.

UCLA scientists have developed a new system that can map the development of brain cells.

One of the latest breakthroughs comes from Dr. Daniel Geschwind and his team at the University of California, Los Angeles (UCLA), who have found a way to track precisely how early-stage brain cells are formed. These findings, published recently in the journal Neuron, shed important light on what had long been considered one of biology’s black boxes—how a brain becomes a brain.

Along with co-lead authors and UCLA postdoctoral fellows Drs. Luis de la Torre-Ubieta and Jason Stein, Geschwind developed a new system that measures key data points along the lifetime of a cell, as it matures from an embryonic stem cell into a functioning brain cell, or neuron. These new data points, such as when certain genes are switched on and off, then allow the team to map how the developing human fetus constructs a functioning brain.

Geschwind is particularly excited about how this new information can help inform how complex neurological conditions—such as autism—can develop. As he stated in a news release:

“These new techniques offer extraordinary promise in the study of autism, because we now have an unbiased and genome-wide view of how genes are used in the development of the disease, like a fingerprint. Our goal is to develop new treatments for autism, and this discovery can provide the basis for improved high-efficiency screening methods and open up an enormous new realm of therapeutic possibilities that didn’t exist before.”

This research, which was funded in part by a training grant from CIRM, stands to improve the way that scientists model disease in a dish—one of the most useful applications of stem cell biology. To that end, the research team has developed a program called CoNTEXT that can identify the maturity levels of cells in a dish. They’ve made this program freely available to researchers, in the hopes that others can benefit. Said de la Torre-Ubieta:

“Our hope is that the scientific community will be able to use this particular program to create the best protocols and refine their methods.”

Want to learn more about how stem cell scientists study disease in a dish? Check out our pilot episode of “Stem Cells in your Face.”

Stem cell stories that caught our eye: need for mature fat, Down syndrome, autism and those sweet pup faces

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Embryonic stem cells and that sweet puppy face. Could altered stem cells give our pups those floppy ears and adorable faces? Research from Humboldt University in Berlin suggests that is the case. They speculate that when people began to domesticate wild animals they were unwittingly breeding for smaller adrenal glands that are responsible for the “fight-or-flight” syndrome. But those glands arise from a group of stem cells in the developing embryo, the neural crest, that is also responsible for many other aspects of the animal including parts of the skull and the ears.

Annika, a member of the author's "pack," shows the floppy ears and narrow face of domestication. The seat on the furniture could be another clue.

Annika, a member of the author’s “pack,” shows the floppy ears and narrow face of domestication. The seat on the furniture could be another clue.

Researchers have noted since Darwin’s time that these signs of “domestication syndrome” with its floppy ears and narrow faces carry across a broad range of domestic animals. The German team said that the genetic alterations of neural crest stem cells could explain this “hodge-podge of traits.”

The research was published in the journal Genetics and got wide pick up with a fun piece on Mashable and a bit more detail about the science in Pacific Standard Magazine.

Stress might make fat go rogue. It is not something dieters will want to hear, but in order to stay healthy your fat stem cells need to mature into adult fat tissue. When they don’t fat can accumulate at high levels in the bloodstream and within existing cells. A team at Boston University suggests that stress plays a role in how the body processes fat by inhibiting the maturation of fat stem cells. They identified two proteins that act as relay switches to regulate the fat stem cells. That signaling pathway now becomes a target for discovering drugs that might improve our handling of fat, even in times of stress. The team published their work in the Journal of Biological Chemistry and HealthCanal picked up the university’s press release.

Support cells linked to Down syndrome. CIRM-funded researchers at the University of California, Davis have found that the errors in nerve development in Down syndrome may be caused by abnormal functioning of the cells that are supposed to support them, the glial cells. The team started by reprogramming skin cell samples from people with Down syndrome into iPS type stem cells. They then matured those cells in two batches, one into neurons and one into glial cells. The nerves did not seem different from normal nerves but the glial cells produced an abnormally high level of a particular protein. When they mixed the two cell types together, that protein appeared to kill off part of the nerves.

What is intriguing, when they treated the mixed cells with a simple antibiotic the nerve damage did not occur. If the protein only has its negative impact on the developing brain, the finding opens up the possibility of preventive treatment for women who find their fetus has the third chromosome distinctive of Down syndrome. The researchers published their findings in Nature Communication and Science Daily ran a story on the work.

Pros and cons of the large autism trial. Using stem cells to try to treat autism provokes a lot of raw emotion in our field. I frequently field questions from desperate mothers wanting to know where they can take the umbilical cord stem cells they have stored in a freezer to treat their child with autism. I tell them about some of the controversies about this treatment and the need for more data before we know how to use the cells right, if there is any chance they can help at all. The Simons Foundation Autism Research Initiative published a well-balanced analysis of the first large clinical trial trying to answer those questions.

The piece has a skeptic rightfully noting that the type of stem cells in cord blood cannot make replacement cells for the poorly functioning nerve cells in people with autism. It also discusses the possibility that those stem cells might stimulate the person’s own cells to make some of the needed repairs. The trial, which will randomly assign patients to stem cell therapy or no therapy, is being led by Duke University’s Joanne Kurtzenburg, who is described by one outside expert as “the right person to do this.” She is a well-known leader in the field and I would love to have some data to share with parents.

CIRM hosted a group of international experts in autism to look at ways stem cells could foster therapies in autism that produced this report. One of the main suggestions was to use iPS type stem cells to model the disease as shown in this video.

Don Gibbons