Comprehensive analyses of brain cell communications based on multiple scRNA‐seq and snRNA‐seq datasets for revealing novel mechanism in neurodegenerative diseases

Author:

Zhang Chunlong1ORCID,Tan Guiyuan1,Zhang Yuxi1,Zhong Xiaoling1,Zhao Ziyan1,Peng Yunyi1,Cheng Qian1,Xue Ke1,Xu Yanjun1,Li Xia1,Li Feng1,Zhang Yunpeng1ORCID

Affiliation:

1. College of Bioinformatics Science and Technology Harbin Medical University Harbin China

Abstract

AbstractAimsComplex cellular communications between glial cells and neurons are critical for brain normal function and disorders, and single‐cell level RNA‐sequencing datasets display more advantages for analyzing cell communications. Therefore, it is necessary to systematically explore brain cell communications when considering factors such as sex and brain region.MethodsWe extracted a total of 1,039,459 cells derived from 28 brain single‐cell RNA‐sequencing (scRNA‐seq) or single‐nucleus RNA‐sequencing (snRNA‐seq) datasets from the GEO database, including 12 human and 16 mouse datasets. These datasets were further divided into 71 new sub‐datasets when considering disease, sex, and region conditions. In the meanwhile, we integrated four methods to evaluate ligand–receptor interaction score among six major brain cell types (microglia, neuron, astrocyte, oligodendrocyte, OPC, and endothelial cell).ResultsFor Alzheimer's disease (AD), disease‐specific ligand–receptor pairs when compared with normal sub‐datasets, such as SEMA4A‐NRP1, were identified. Furthermore, we explored the sex‐ and region‐specific cell communications and identified that WNT5A‐ROR1 among microglia cells displayed close communications in male, and SPP1‐ITGAV displayed close communications in the meninges region from microglia to neurons. Furthermore, based on the AD‐specific cell communications, we constructed a model for AD early prediction and confirmed the predictive performance using multiple independent datasets. Finally, we developed an online platform for researchers to explore brain condition‐specific cell communications.ConclusionThis research provided a comprehensive study to explore brain cell communications, which could reveal novel biological mechanisms involved in normal brain function and neurodegenerative diseases such as AD.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology

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