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Stem cell models can help unravel the complex biology behind some psychiatric disorders-ScienceDaily
Researchers at Mount Sinai Medical College have identified disease-risk mutations in human neurons that may help provide insights into the underlying biological mechanisms of neuropsychiatric disorders such as autism and schizophrenia. We applied a new stem cell model for mapping.
Of the team In vitro Cellular model, described in the May 31 issue Cell reportIs designed to enable future researchers to elucidate disease mechanisms, including genome-wide association studies (GWAS) that characterize various risk alleles of psychiatric disorders (common genetic variation that poses a risk). This study may lead to improved diagnosis for detecting mental illness years before symptoms appear in patients.
This study focuses on the mapping of cis-regulatory elements in human neurons that may be associated with the heritability of psychiatric disorders. Cis-regulatory elements such as promoters and enhancers are important components of gene regulatory networks because they are non-coding DNA sequences that regulate gene expression. Previous genetic studies have revealed a significant enrichment of common mutations in cis-regulatory elements, including those associated with autism spectrum disorders, schizophrenia, and bipolar disorder.
“While common risk variants can shed light on the underlying molecular mechanism, it is still difficult for scientists to identify the causative variant,” said an assistant professor of neuroscience at Mount Sinai School of Medicine. Yes, said Dr. Nanyang, senior author of the study. “This is because cis-regulatory elements, especially enhancers, depend on cell type and activity. Normally, researchers can only use postmortem brain samples in which neurons are inactive. As a result, enhancers that only respond. Our approach is to map the cis-regulatory elements of human neurons derived from pluripotent stem cells, which can be affected by different types of neuropsychiatric disorders. It can replicate neurons in the brain and conduct mechanistic studies of human genetic mutations, not accessible from other types of human samples. “
In recent years, GWAS have identified hundreds of genetic regions associated with psychiatric disorders, but it has been difficult to understand the pathophysiology of the disease. A functional genomics approach developed by Dr. Yang and her team will help solve the effects of patient-specific mutations across cell types, genetic backgrounds, and environmental conditions using stem cell models. This unique approach effectively lays the foundation for translating risk variants into genes, genes into pathways, and pathways into circuits, revealing synergistic relationships between disease risk factors in the brain and between cell types. increase.
“Our research seeks to decipher highly complex genetic insights and translate them into medically practical information,” said the Black Family Stem Cell Institute, Friedman Brain Institute, and Ronald of Alzheimer’s disease. Dr. Yang, a member of the M. Loeb Center, says. Within the Mount Sinai Health System. “It means improving our diagnostic capabilities, predicting clinical trajectories, and identifying presymptomatic points for therapeutic interventions in psychiatric disorders.”
Dr. Yang believes that her team’s research will bring significant benefits to the research community by characterizing cell-type-specific and activity-regulated gene expression patterns in human cell-derived neurons. “Our data will help us select the relevant cell types of the conditions to further elucidate the molecular mechanism of disease throughout the genome,” she points out. “And that could lead to the development of biomarkers that may detect neuropsychiatric disorders years before they appear in patients, but there is still time to delay or perhaps prevent them.”
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