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Rare cell types can have undue effects on
human health.
Previous research has suggested that a subset of astrocytes — the astrocytes in the brain and spinal cord — may be responsible for multiple sclerosis (MS), a disease
in which the immune system attacks the covering that protects nerves.
But finding these rare cells isn't an easy task—to pinpoint them, researchers need to identify unique surface markers that distinguish these culprit cells from the rest
.
Single-cell RNA sequencing can help find them, even without distinguishing surface markers, but this technique can become very expensive
.
To address this problem, a team led by researchers at Brigham and Women's Hospital, one of the founding members of the Brigham Health Care System, developed a FIND-seq that combines nucleic acid cytometry, microfluidics, and droplet classification to isolate and analyze rare cells
of interest based on the expression of mRNA biomarkers detected by digital droplet PCR.
Using this approach, the team analyzed in detail the astrocytes population
that drive inflammation and neurodegeneration of the central nervous system.
When used in combination with other tools, FIND-seq identified signaling pathways controlled by the mineralocorticoid receptor NR3C2 and nuclear receptor co-inhibitory factor 2, which play an important role
in the development of disease-causing astrocytes in mice and humans.
In another study, researchers used FIND-seq to determine the mechanisms
by which HIV is "hidden" in immune cells in patients receiving antiretroviral therapy.
Dr.
Francisco Quintana, corresponding author of BWH's Department of Neurology, said: "These findings identify new targets for therapeutic interventions for neurological diseases such as MS
.
" The team is working to develop new small molecules that could be used to treat this pathway
.
FIND-Seq article and read about its use in HIV research in a companion paper published in
the same issue.
Original search:
1.
Identification of astrocyte regulators by nucleic acid cytometry
2.
HIV silencing and cell survival signatures in infected T cell reservoirs