Genomic ‘shake up’ allows cells to play the roles of others

Variability in how DNA is packaged allows cells to take on the identity of different cell types. Researchers from the University of Chicago (IL, USA) have reported that unstable, or ‘noisy’, chromatin enables cells to take on different roles in the body. This flexibility can support the immune system but could also explain how tumors form from previously healthy cells. All cells in the body contain the same DNA, but different cells will express different genes needed to generate specialized cells, such as the liver or lungs. Chromatin structure and accessibility determine gene expression, as it is usually tightly regulated to sequester regions that encode other cell fates. “Each individual cell does not express the entire genome. Instead, they express only a unique subset of the tissue-specific genes at any given snapshot,” explained Andrew Koh, Assistant Professor of Pathology at the University of Chicago. "There's a great deal of heterogeneity, so we thought that it was really important to look cell–by–cell to uncover the mechanisms that allow the activation of each subset of tissue-specific genes.” To investigate this heterogeneity, Koh and his team focused on medullary thymic epithelial cells (mTECs), which play a key role in training the immune system to avoid autoimmunity. They isolated mTECs from both mice and a human patient and sorted them utilizing fluorescence-activated cell sorting. Koh, lead author Noah Gamble and the team leveraged RNA sequencing to study gene expression and single-cell multiome sequencing to analyze both gene expression and chromatin accessibility within individual cells. They also used CUT&RUN and ChIP-seq data to investigate protein–DNA interactions, providing a comprehensive view of the cells' molecular profiles. Accelerating antibody development with a novel platform The oPool+ display platform combines technologies to make and test large numbers of antibodies at once.