Exploring autism through stem cell technology

The 'magic' of reprogramming cells

Lizarraga and her team focus much of their research on chromatin—the material that chromosomes of organisms are composed of—which consists of protein and DNA. Genetic findings suggest that there is an overrepresentation of chromatin regulatory genes that have mutations associated with autism spectrum disorders. But there’s a catch—one single chromatin regulatory gene can regulate the expression of hundreds or even thousands of other genes at the same time. Therefore, a single mutation in a chromatin regulatory gene could disrupt multiple processes that are essential for proper neuronal development. This makes it much more challenging than studying other genes.

To do their work, Lizarraga’s team harnesses the power of stem cell technology, where they take human adult cells and reprogram them (by overexpressing four transcription factors). “The re-programming process (and the quality control testing) takes about four to six months,” says Lizarraga, “but once you have the stem cells, they can become any other cell in the body. It's like magic.”

Lizarraga’s lab makes human stem cell-derived neurons in culture, which they call a two-dimensional system (cells are grown in dish as a single layer), but a future goal is the creation of three-dimensional cultures called organoids or mini brains. “Being able to have a model where you can actually mimic the early stages of human neuronal development is really powerful,” she says. “You can ask so many questions that you couldn't ask otherwise.”

Strength in numbers

Another great advantage to doing this work at Brown is that there are multiple labs using stem cells to study everything from Alzheimer’s disease to epilepsy and autism-related disorders. They are all asking different questions, but together they are moving the needle of discovery.

The collaboration in Brown’s Center for Translational Neuroscience is going to be really important as we move what we find at the bench to the clinic, Lizarraga says. “That is what drives me every day.”