How a stem cell forms a neuron

CIRM grantees at Sanford-Burnham have published another paper using an embryonic stem cell model to understand one of the earliest steps in human nervous system development. (We've blogged about their work before here.)

The group led by Alexey Terskikh has been trying to understand how a group of cells called the neural crest form nerves, skin, bone and muscle. This process has been somewhat mysterious because it happens at such an early stage in development. Scientists can't exactly peer into a woman's womb to see the process unfold.

That's where embryonic stem cells come in. These cells can form all cell types in the body, including neural crest. On their blog, Sanford-Burnham quotes first author on the May 5 Cell Stem Cell study Flavio Cimadamore:

“Neural crest cells are notoriously difficult to study in humans because of their very early and transient nature – a woman is usually not even yet aware of her pregnancy when they start to migrate and differentiate. So here we took advantage of an embryonic stem cell-based model of human neural crest previously developed in our lab to get a better understanding of the molecular pathways that control the differentiation potential of such cells in humans.”

In the current work, the team found that neural crest cells with a gene called SOX2 turned on can go on to form neurons. Those without it can't. That's critical information for people who are trying to understand diseases that arise from neural crest cells that go awry during development. Microphthalmia and CHARGE syndrome are two rare but debilitating childhood diseases that could benefit from knowing more about how the neural crest normally develops.

In the blog entry, Terskikh said:

"We hope this finding will be useful to researchers studying neural crest development and stem cell differentiation.”

CIRM funding: Alexey Turskikh (RS1-004661); Flavio Cimadamore (TG2-01162)
Cell Stem Cell, May 5

A.A.

Stem cells reveal elusive developmental steps, origins of disease

Our colleagues at Sanford-Burnham Medical Research Institute have a post today on their excellent blog about work by CIRM grantee Alexey Turskikh, published in a recent issue of PLoS ONE. The teams work is another example of how embryonic stem cells can help scientists understand early events in development.

The team has been interested in a group of cells called the neural crest, which eventually form nerves, skin, bone and muscle in the developing embryo. If scientists could understand this important developmental step they could also understand diseases that result when those steps go awry. The problem is that they can't very well monitor the process in a developing human.

That's where embryonic stem cells come in. The team developed a method of maturing embryonic stem cells into neural crest cells. Sanford-Burhnam writes:

With this method, Dr. Terskikh’s group and others will now be able to better study what defines human neural crest stem cells, how they migrate during development, how they differentiate into other cell types, and the mechanisms that guide these processes. What’s more, producing workable quantities of neural crest stem cells in the laboratory might allow scientists to generate more of the tissues that they become – including clinically-relevant cell types like skin cells or neurons.

According to Dr. Maurer, one of the study’s co-authors, “This research allows for fast and easy access to an important developmental structure and one of the best examples of a particular stage in development – the epithelial-mesenchymal transition (EMT). Since EMT is now a hot topic in tumorigenesis and cancer progression, these cells might help us better understand the molecular mechanisms governing that process. ”

There's a long path from find the cells to developing cures, but you don't get to the end of a race without taking the first step.

CIRM Funding: Alexey Turskikh (RS1-00466-1)

- A.A.