Mapping secretome-mediated interaction between paired neuron-macrophage single cells

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Neuron-immune interactions in the central nervous system are crucial but poorly understood at the single-cell level.
• Secreted factors mediate these interactions, influencing cell functions in health and disease.
• Alzheimer's disease (AD) involves complex neuroinflammatory processes.

Purpose of the Study:

• To map and analyze the secretomes of paired neuron-immune single cells.
• To investigate how amyloid beta (Aβ) protein influences neuron-immune secretome profiles in an AD model.
• To identify potential biomarkers for AD based on cellular secretions.

Main Methods:

• Developed a spatially patterned antibody barcode microchip for high-throughput, paired single-cell secretome analysis.
• Analyzed 12 secretomes, including cytokines, neurotrophic factors (NFs), and neuron-derived exosomes (NDEs).
• Utilized human cell lines for neuron-macrophage and neuron-microglia co-culture models, including an Aβ_1-42-induced AD model.

Main Results:

• Neuron-macrophage interaction attenuated neuron secretion, while neuron-microglia interaction generally enhanced it.
• In the AD model, both interactions increased cytokines and NDEs while decreasing NFs.
• Significantly higher NDE levels were observed in AD patient serum compared to controls, validating in vitro findings.
• Resolved heterogeneity in single-neuron cell secretions, showing reduced NDE/NF secretion and overall attenuation after Aβ_1-42 exposure.

Conclusions:

• The study successfully mapped diverse secretomes from paired neuron-immune single cells.
• Provides insights into the complex secretome network governing neuron-immune communication in physiological and AD conditions.
• Highlights NDEs as potential circulating biomarkers for Alzheimer's disease.