Decoding secretor-mediated neuron-immune cell interaction networks

Recently, Lu Yao's team, a researcher in the single-cell analysis research group of the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, used single-cell multi-secreted factor detection technology to realize the analysis
of neuro-immune cell interaction networks.

As the global population gradually enters the aging stage, neurodegenerative diseases are becoming one of
the major diseases threatening human health.
Nerve cells are directly related to neurodegenerative diseases, but nerve cells do not exist in isolation, and nerve cells need to transmit and interact with other cells through physical contact, signal exchange of biomolecules, etc.
, to complete biological functions
collaboratively.

In recent years, studies have shown that there is a close interaction
between the nervous system and the immune system.
Immune cells in the brain play a key role
in shaping and regulating the nerve function of nerve cells.
Although mass spectrometry, PCR, and single-cell/single-nucleic acid sequencing (sc-RNAseq/snRNA-seq) have been used to resolve neuro-immune cell interactions at the population cell level or at the single-cell level, it is unclear
how neuro-immune cells mediate interactions through multiple secreted factor signals in physiological and pathological states 。 The analysis of the neuro-immune cell interaction network can provide a clearer and deeper understanding of the basic biological process of neuro-immune cell communication, and is expected to lay an important preliminary foundation
for analyzing the development of neurodegenerative diseases and discovering the disease diagnostic markers of neurodegenerative diseases.

In this study, the detection technology of single-cell multi-secreted factors (PNAS, 2019) was used to realize the simultaneous detection of 12 secreted factors of a single nerve cell, including cytokines, neurotrophic factors and neurogenic exosomes, and revealed the heterogeneity and correlation of multiple secreted factors of nerve cells.
Studies applied to neuro-immune paired single-cell interactions have found that infiltrating macrophages and resident macrophages (microglia) have different effects on the regulation of the secretory function of nerve cells, for example, infiltrating macrophages generally tend to inhibit nerve cell secretion of exosomes, while microglia promote nerve cell secretion of exosomes
.
Further, it was found that the interaction of nerve cells with macrophages or microglia in the Alzheimer disease model led to increased
secretion of pro-inflammatory cytokines.
This study provides new technical support for the exploration of the brain microenvironment, and is expected to provide data reference
for the occurrence, development and discovery of markers of neurodegenerative diseases.

Recently, the relevant research results were published in the Proceedings of the National Academy of Sciences (PNAS
) under the title of Mapping secretome-mediated interaction between paired neuron-macrophage single-cells.
The research work has been supported
by the National Natural Science Foundation of China and the Youth Innovation Promotion Association of the Chinese Academy of Sciences.