NYSCF Innovator Uses Stem Cells To Uncover Genetic Abnormalities in Schizophrenia
Schizophrenia is often studied by analyzing the brains of patients after they’ve passed away. These types of studies usually contain small sample sizes and focus on identifying large, rare variants in the genome rather than smaller, more common variants that may also drive disease pathology.
Stem cells allow researchers to collect blood or skin samples from living patients and turn them into the brain cells affected by the disease—neural progenitor cells (NPCs) and neurons. Researchers can then examine these cells for abnormalities and clues to the disease. This ability makes stem cell-driven research a good complement to studies of postmortem brains. However, previous stem cell research on schizophrenia has focused mostly on finding those large, rare variants, similar to postmortem research.
In a new study published in Nature Communications, a team of researchers at the Icahn School of Medicine at Mount Sinai, including NYSCF — Robertson Investigator Kristen Brennand, PhD, were interested in examining whether stem cell-derived neurons and NPCs showed the same genetic variants (both rare and common) as postmortem brains from schizophrenia patients. The researchers took samples of skin cells from 16 patients with childhood-onset schizophrenia and 12 matched controls, and reverted these cells back into stem cells, then reprogrammed these stem cells into neurons and NPCs. The reprogrammed cells originally taken from schizophrenia patients showed the same transcriptional signatures (or underlying biology) as cells taken from postmortem patients, indicating that the stem cell-derived brain cells successfully recapitulated the disease and identifying possible biological variants that contribute to its onset.
The researchers were also able to refine their protocol for creating these neurons and NPCs—reducing the amount of variation that usually results from cell differentiation. As the protocol was improved, the stem cell-derived neurons and NPCs better matched the characteristics of the cells from postmortem brains. To further maximize accuracy, the researchers recommend that future studies involving stem cells use cell lines from as many individuals as possible rather than generating multiple cell lines from the same individual.