In a new study out this month, scientists at the Lieber Institute showed for the first time the role of specific cell populations in genetic risk for schizophrenia that may have otherwise been overlooked. This is the first study to show how variation in the genome effects unique cell populations. The paper, “Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk,” was published in the journal Nature Neuroscience.
Using laser capture microdissection (LCM) to isolate a specific cell population in the hippocampus critical to memory, researchers were able to identify unique gene expression associations not previously seen in analyses of homogenate tissue samples. Additionally, in one of the most comprehensive transcriptome-wide association studies to date, they found many schizophrenia genetic risk effects that were missed in bulk tissue analysis. These results highlight the significance of strategies like LCM to complement homogenate and single-nucleus analyses of human brain tissue.
The dentate gyrus cells isolated from the hippocampus are the first cells of the memory circuit and are some of the only cells known to regenerate throughout life. Interrogation of these cells could provide critical insight not only in schizophrenia but in the aging process as well. Deeper analyses of specific cell populations in the brain using techniques like LCM will further our understanding of the molecular mechanisms of brain disorders that could one day lead to potential therapeutic targets.