Complex brain circuitry revealed using new single-cell sequencing technology
PHOENIX, Ariz., and Menlo Park, Calif. — June 28, 2018 — The complexity of the human brain presents scientists with immense challenges as they try to find new treatments for a host of diseases and conditions. But the advent of a new technology known as single-cell RNA sequencing is opening a window into how the brain works.
Researchers at the Translational Genomics Research Institute (TGen) and a Silicon Valley startup called Circuit Therapeutics Inc. have combined to look deep inside the brain at a structure known as the striatum, which not only is responsible for controlling how we move, but also contributes to the brain's decision-making and the initiation of action.
Nearly 95 percent of the cells that make up the striatum are known as medium spiny neurons (MSN), whose health or malfunction is associated with many psychiatric and neurodegenerative diseases, including Parkinson's disease, Huntington's disease, schizophrenia, drug addition and ADHD.
In one of the first investigations of its kind, TGen and Circuit Therapeutics have developed exacting methods for examining these MSN cells, and in the process identified a specific gene known as Chrm4 as one of several potential therapeutic drug targets, according to a study published in the journal Frontiers in Cellular Neuroscience.
"Understanding the molecular composition and gene expression of individual MSN cells are of critical importance to gaining insights into how they work and how we can identify drug targets to treat neurological dysfunctions," said Dr. Matt Huentelman, TGen Professor of Neurogenomics. "In this study, we analyzed and simplified methods for isolating single MSN cells in the striatum, using newly available technology to examine them with unprecedented resolution."
By using single-cell RNA sequencing, the team redefined previous understandings of how MSN cells work, and added to the list of MSN marker genes previously discovered using older technologies that analyzed gene expression by studying bulk portions of striatal tissue.
"Understanding the molecular properties of neural circuitry in the brain is of great interest to neuroscience drug discovery," said Dr. Thomas Portmann, Director of Neurobiology and Transcriptomics at Circuit Therapeutics Inc. "Being able to understand how individual cells form key neural circuits is rapidly advancing our knowledge about the molecular signatures of the brain, and about druggable targets for development of future therapies."
The study — A Guide to Single-Cell Transcriptomics in Adult Rodent Brain: The Medium Spiny Neuron Transcriptome Revisited — published June 15 in Frontiers in Cellular Neuroscience.
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with neurological disorders, cancer, diabetes, and infectious diseases, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. TGen is affiliated with City of Hope, a world-renowned independent research and cancer and diabetes treatment center: http://www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. For more information, visit: http://www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.
TGen Senior Science Writer
About Circuit Therapeutics Inc.
Circuit Therapeutics Circuit Therapeutics is the world leader in optogenetics — a transformational technology that gives researchers and clinicians the ability to control neural activity with light. Optogenetics enables unparalleled specificity and temporal control of neural circuits, and has allowed Circuit to create an unrivaled platform for discovery and validation of novel drug targets. Founded by Karl Deisseroth, Rob Malenka, Scott Delp, Thomas Sudhof, and Karoly Nikolich, Circuit Therapeutics is based in Menlo Park, California. For more information, please visit http://www.circuittx.com
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