Breakthrough method yields trove of neuron subtypes, gene regulators

Molecular profiling may be key to compiling brain’s “parts list”.

What

With funding from the National Institutes of Health's BRAIN Initiative, researchers have discovered a trove of neuronal subtypes and gene regulators, using a new method they developed. It allows for the discovery of subtypes based on their unique profiles of molecular switches that regulate gene expression within the cell. This opens the door to potentially discovering changes in such profiles linked to brain disorders, say the researchers.

The new method profiles molecular changes to the DNA (the genetic blueprint) known as epigenetic regulation. This is accomplished by sequencing the neuronal genomes in a way that detects modified DNA, producing a signature called the methylome. It turns out that each cell type has a unique methylome, even though the DNA itself is the same in every cell.

In the frontal cortex, the researchers identified 16 neuronal subtypes in mice and 21 subtypes in humans. Neurons that slow down brain activity were found to share more regulatory elements across mice and humans than neurons that speed up brain activity. Some of the latter excitatory neuron types appear to be unique to humans.

Who

Andrea Beckel Mitchener, Ph.D., NIMH Functional Neurogenomics Program

When

August 10, 2017

Articles

ingle-cell methylomes identify neuronal subtypes and regulatory elements in mammalian brain. Luo D, Keown CL, Kurihara L, Zhou J, He Y, Li J, Castanon R Lucero J, Nery JR, Sandoval JP, Bui B, Sejnowski TJ, Harkins TT, Mukamel EA, Behrens MM, Ecker JR. Science 2017 Aug 10

Grants

MH105985, MH112161, HG009274, MH020002

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