The brain’s prefrontal cortex, which gives us our ability to solve problems and plan ahead, contains billions of cells. But understanding the large diversity of cell types in this critical region, each with unique genetic and molecular properties, has been challenging. Scientists have known that much of this diversity results from epigenetics as well as how epigenetic features ultimately fold up within chromosomes to affect how genes are expressed.
The study developing a method to simultaneously analyze how chromosomes, along with their epigenetic features, are compacted inside of single human brain cells. A collaborative team of scientists from the Ecker and Dixon labs combined two different analysis techniques into one method, which enabled them to identify gene regulatory elements in distinct cell types.
Diversity of cell types
DNA is packing within structures calling chromosomes in a cell’s nucleus can play a critical role in cellular function. And how DNA is ultimately folding depends on which sections of DNA need; to interact with each other and which need to be easily accessible to cellular machinery. The structure of chromosomes acts as a sort of cellular fingerprint; although different cell types have the same sequence of DNA, they have different chromosome structures to organize that DNA.
When doing the experiments separately, however, researchers can’t determine; how chromosome structure and methylation patterns might be related. It has been unclear whether each subset of chromosome structures corresponds to a subset of methylation patterns. Or whether the two datasets, when combined, reveal more nuanced subtypes of cells.
But the method that examining these features in single cells allows scientists to use certain; analytical tricks to directly study tissue samples and resolve chromosome structure; and DNA methylation in all the different cell types in the tissue. Studying these features can vary a lot between cell types and there’s value; in having both types of information together from the same cells; a Helmsley-Salk Fellow and co-corresponding author.
It really opens up our ability to understand what regulatory sequences; are affecting which genes across a wide variety of cell types and tissues. But the researchers say that, by studying chromosome folding in actual human tissues and resolving distinct cell types; these methods may allow them to link disease-causing genetic variants with the genes they regulate; BUT which may tell them more about why certain variants contribute to diseases and offer insights into how to best treat them.