Abstract

High-throughput mapping of neuro-glial interactions

Grant de Jong, Jarrod Shilts, Jing Eugene Kwa, Dr. Omer Bayraktar

While glial cells are well understood to be more than simply the nervous system “glue” that their eponym suggests, they are often underrepresented in neurogenomics studies. Despite roughly equivalent numbers of glia and neurons, it is not well understood how these cells interact with neurons and other brain cells to facilitate healthy brain function. Recently, researchers at the Wright Lab have developed a new high-throughput brain receptor interaction screen with the aim of elucidating neuron-glia communication. Using the resulting list of protein-protein interactions (PPIs), the focus of this project was to integrate these new PPIs with single-nucleus RNA-sequencing (snRNA-seq) data to infer patterns of cell-cell communication between neurons and glia. This was initially accomplished by surveying the interaction landscape in healthy cortical tissue. Although this dataset showed a high degree of promiscuity among brain interactions, novel interactions were found to be more frequent in non-homeostatic glial subtypes. Additionally, many of these novel interactions exhibited significant enrichment in microglia and astrocytes, specifically. To understand how these interactions were modulated in different neurological contexts, Alzheimer’s disease (AD) data from the prefrontal cortex and amyotrophic lateral sclerosis (ALS) data from the primary motor cortex were also examined. These analyses showed subtype-specific variance in the extent of PPI expression, as well as several novel PPIs, which showed significant divergence in expression under AD. Overall, these analyses will provide a starting point for further assessment of the neuron-glial interaction landscape, for which the inclusion of additional brain regions and developmental contexts will be informative.

Supplemental figures:

supplemental_figures_grant_de_jong.pdf

Data sources

Prefrontal cortex Alzheimer’s data:

Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease

Leng K, Li E, Eser R, Piergies A, Sit R, Tan M, Neff N, Li SH, Rodriguez RD, Suemoto CK, Leite RE. Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease. Nature neuroscience. 2021 Feb;24(2):276-87.

Prefrontal cortex healthy data:

Unpublished

Jing Eugene Kwa, Omer Bayraktar

Primary motor cortex data (ALS and healthy):

Unpublished

Jing Eugene Kwa, Omer Bayraktar