Rare cell types can have a disproportionate impact on human health. Previous studies have suggested that a subset of astrocytes (star-shaped cells in the brain and spinal cord) may be responsible for multiple sclerosis (MS). It is a disease in which the immune system attacks the protective coverings of nerves. To identify them, researchers must identify unique surface markers that can distinguish these causative cells from others.
Single-cell RNA-sequencing can help find them without discernible surface markers, but this technique can be very expensive. To address this problem, a team led by researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham Health Care System, developed FIND-seq. Interest based on expression of mRNA biomarkers detected by digital droplet PCR. Using this method, the team dissected astrocyte populations that cause central nervous system inflammation and neurodegeneration.
Used in combination with other tools, FIND-seq is regulated by the mineralocorticoid receptor NR3C2 and nuclear receptor corepressor 2, which play critical roles in mouse and human pathogenic astrocyte development identified signaling pathways. In another study, researchers used FIND-seq to identify the mechanism HIV uses to “hide” in the immune cells of patients treated with antiretroviral therapy.
These findings identify new targets for therapeutic intervention in neurological disorders such as MS. ”
Dr. Francisco Quintana, Lead Author, BWH Neurology
The team is working to develop new small molecules that can be used to therapeutically target this pathway.
For more information on FIND-Seq, please refer to the following papers. Nature Also, about the application to HIV research in a related paper published in the same issue.
Brigham and Women’s Hospital
Clark, IC, and others. (2023) Identification of astrocyte regulators by nucleic acid cytometry. Nature. doi.org/10.1038/s41586-022-05613-0.