Stem-cell derived, developing human neurons.

Researchers from Brigham and Women’s Hospital (BWH) have genetically engineered human stem cells to harbor mutations in a known risk gene for mental illnesses such as schizophrenia, bipolar disorder, depression and autism. A rare, strong mutation in this gene – known as DISC1 – was originally detected in a Scottish family in which members had a range of psychiatric disorders. Common, weaker mutations have also been found in the gene and tied to risk of mental illness. Engineering these mutations in stem cells in the lab could yield new insights into how genetic mutations may predispose a person to mental illness and why so many different mental illnesses may share common genetic roots.

“I am excited about this study, as it gives us a window into what could be going wrong in human fetal brain development that leads to later onset of mental illness,” said corresponding author Tracy Young-Pearse, PhD, an associate scientist in the Department of Neurology and Ann Romney Center for Neurologic Diseases at BWH and an assistant professor at Harvard Medical School.

The team is among only a handful of labs to have successfully modeled mental illness with stem cells.

In their paper appearing in Cell Reports, Young-Pearse and her colleagues direct stem cells to become brain cells in the dish. Using the genetic engineering tools TALENS and CRISPR-Cas9 to disrupt DISC1, the researchers find that the mutant cells had trouble making a particular kind of neural progenitor cell found in the human fetal cerebral cortex. Their work points to gene candidates for future study and offers a model for the study of neurodevelopment and mental illness.