Scientists at the Icahn School of Medicine at Mount Sinai are embarking on one of the largest single-cell transcriptomic studies aimed at understanding alternative splicing events in neurodegenerative diseases, including Alzheimer’s and Parkinson’s. The research effort, which involves analyzing more than 10 million cells from over 1,000 patient samples, is expected to shed light on lesser-studied molecular processes that may contribute to disease progression.
The study will focus specifically on peripheral blood mononuclear cells donated by patients with confirmed diagnoses. Using high-throughput sequencing techniques, researchers hope to uncover patterns of alternative splicing, a post-transcriptional process where RNA is edited to produce different proteins, that could influence how these diseases develop and progress.
“Most previous studies have emphasized genetic risk factors, but relatively few have examined the role of RNA splicing in neurodegenerative disease” said Dr. Towfique Raj, who leads the research team. Raj is a core faculty member at the Ronald M. Loeb Center for Alzheimer’s Disease and heads the Laboratory for Functional Genomics at Mount Sinai.
“By looking at splicing events at the single-cell level and at this scale, we can begin to build more accurate models of disease mechanisms” Raj added. “This could be key to understanding why diseases like Alzheimer’s and Parkinson’s progress differently across individuals.”
To process the large volume of samples, Mount Sinai is partnering with Seattle-based biotech firm Parse Biosciences. Samples prepared at Mount Sinai will be sent to Parse’s GigaLab, a facility designed for large-scale single-cell RNA sequencing.
Parse Biosciences’ Chief Technology Officer, Dr. Charlie Roco, said the partnership allows the company’s infrastructure to be used in support of complex, high-impact biomedical research. “The speed and scale of GigaLab are designed to accelerate studies like this one, helping researchers reach insights more quickly” Roco noted.
Mount Sinai’s research team has long focused on the molecular underpinnings of neurodegenerative disorders, including ALS, with an emphasis on integrating genomic and transcriptomic data. The current project stands out for its scope and potential to reveal new molecular pathways involved in disease onset and severity.