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

作者：Zhang, Chunlong; Tan, Guiyuan; Zhang, Yuxi; Zhong, Xiaoling; Zhao, Ziyan; Peng, Yunyi; Cheng, Qian; Xue, Ke; Xu, Yanjun; Li, Xia; Li, Feng^*; Zhang, Yunpeng^*

来源：CNS Neuroscience & Therapeutics, 2023, 29(10): 2775-2786.

DOI：10.1111/cns.14280

• Alzheimer's disease
• bioinformatic platform
• brain
• cell communications

AimsComplex 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.

• 单位
  哈尔滨医科大学