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

Neuron-immune interaction through secreted factors contributes significantly to the complex microenvironment in the central nervous system that could alter cell functionalities and fates in both physiological and pathological conditions, which remains poorly characterized at the single-cell level. H...

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Autores principales: Deng, Jiu, Ji, Yahui, Zhu, Fengjiao, Liu, Lina, Li, Linmei, Bai, Xue, Li, Huibing, Liu, Xianming, Luo, Yong, Lin, Bingcheng, Lu, Yao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636946/
https://www.ncbi.nlm.nih.gov/pubmed/36288285
http://dx.doi.org/10.1073/pnas.2200944119
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author Deng, Jiu
Ji, Yahui
Zhu, Fengjiao
Liu, Lina
Li, Linmei
Bai, Xue
Li, Huibing
Liu, Xianming
Luo, Yong
Lin, Bingcheng
Lu, Yao
author_facet Deng, Jiu
Ji, Yahui
Zhu, Fengjiao
Liu, Lina
Li, Linmei
Bai, Xue
Li, Huibing
Liu, Xianming
Luo, Yong
Lin, Bingcheng
Lu, Yao
author_sort Deng, Jiu
collection PubMed
description Neuron-immune interaction through secreted factors contributes significantly to the complex microenvironment in the central nervous system that could alter cell functionalities and fates in both physiological and pathological conditions, which remains poorly characterized at the single-cell level. Herein, using a spatially patterned antibody barcode microchip, we realized the mapping of 12 different secretomes, covering cytokines, neurotrophic factors (NFs), and neuron-derived exosomes (NDEs) from high-throughput, paired single cells (≥ 600) simultaneously under normal conditions and an Alzheimer’s disease (AD) model induced with amyloid beta protein 1-42 (Aβ(1–42)). We applied the platform to analyze the secretion profiles from paired neuron–macrophage and neuron–microglia single cells with human cell lines. We found that pairwise neuron–macrophage interaction would trigger immune responses and attenuate neuron cells’ secretion, while neuron–microglia interaction generally results in opposite outcomes in secretion. When neuron cells are induced with Aβ(1–42) protein into the AD model, both neuron–macrophage and neuron–microglia interactions lead to increased cytokines and NDEs and decreased NFs. Further analysis of AD patients’ serum showed that NDEs were significantly higher in patients’ samples than in the control group, validating our observation from the interaction assay. Furthermore, we resolved previously undifferentiated heterogeneity underlying the secretions from single-neuron cells. We found that the NDE and NF secretion was less dependent on the paracrine signaling between one another and that secretions from neuron cells would attenuate after differentiation with Aβ(1–42). This study demonstrates the mapping of the different secretomes from paired neuron-immune single cells, providing avenues for understanding how neurons and immune cells interact through the complex secretome network.
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spelling pubmed-96369462023-04-26 Mapping secretome-mediated interaction between paired neuron–macrophage single cells Deng, Jiu Ji, Yahui Zhu, Fengjiao Liu, Lina Li, Linmei Bai, Xue Li, Huibing Liu, Xianming Luo, Yong Lin, Bingcheng Lu, Yao Proc Natl Acad Sci U S A Physical Sciences Neuron-immune interaction through secreted factors contributes significantly to the complex microenvironment in the central nervous system that could alter cell functionalities and fates in both physiological and pathological conditions, which remains poorly characterized at the single-cell level. Herein, using a spatially patterned antibody barcode microchip, we realized the mapping of 12 different secretomes, covering cytokines, neurotrophic factors (NFs), and neuron-derived exosomes (NDEs) from high-throughput, paired single cells (≥ 600) simultaneously under normal conditions and an Alzheimer’s disease (AD) model induced with amyloid beta protein 1-42 (Aβ(1–42)). We applied the platform to analyze the secretion profiles from paired neuron–macrophage and neuron–microglia single cells with human cell lines. We found that pairwise neuron–macrophage interaction would trigger immune responses and attenuate neuron cells’ secretion, while neuron–microglia interaction generally results in opposite outcomes in secretion. When neuron cells are induced with Aβ(1–42) protein into the AD model, both neuron–macrophage and neuron–microglia interactions lead to increased cytokines and NDEs and decreased NFs. Further analysis of AD patients’ serum showed that NDEs were significantly higher in patients’ samples than in the control group, validating our observation from the interaction assay. Furthermore, we resolved previously undifferentiated heterogeneity underlying the secretions from single-neuron cells. We found that the NDE and NF secretion was less dependent on the paracrine signaling between one another and that secretions from neuron cells would attenuate after differentiation with Aβ(1–42). This study demonstrates the mapping of the different secretomes from paired neuron-immune single cells, providing avenues for understanding how neurons and immune cells interact through the complex secretome network. National Academy of Sciences 2022-10-26 2022-11-01 /pmc/articles/PMC9636946/ /pubmed/36288285 http://dx.doi.org/10.1073/pnas.2200944119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Physical Sciences
Deng, Jiu
Ji, Yahui
Zhu, Fengjiao
Liu, Lina
Li, Linmei
Bai, Xue
Li, Huibing
Liu, Xianming
Luo, Yong
Lin, Bingcheng
Lu, Yao
Mapping secretome-mediated interaction between paired neuron–macrophage single cells
title Mapping secretome-mediated interaction between paired neuron–macrophage single cells
title_full Mapping secretome-mediated interaction between paired neuron–macrophage single cells
title_fullStr Mapping secretome-mediated interaction between paired neuron–macrophage single cells
title_full_unstemmed Mapping secretome-mediated interaction between paired neuron–macrophage single cells
title_short Mapping secretome-mediated interaction between paired neuron–macrophage single cells
title_sort mapping secretome-mediated interaction between paired neuron–macrophage single cells
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636946/
https://www.ncbi.nlm.nih.gov/pubmed/36288285
http://dx.doi.org/10.1073/pnas.2200944119
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