单细胞 RNA 测序揭示星形胶质细胞的异质性.

BACKGROUND: Astrocytes are the most abundant cells in the central nervous system, and various subsets of astrocytes are heterogeneous, performing a variety of special functions. Single-cell RNA sequencing (scRNA-seq) technology developed in recent years has extended our understanding of astrocyte heterogeneity from the perspective of transcriptome profiling. OBJECTIVE: To summarize the heterogeneity of scRNA-seq technology in different time and space, and pathological states and expand our knowledge of astrocyte heterogeneity on both molecular and functional levels. METHODS: The relevant articles on astrocyte heterogeneity and scRNA-seq were searched on PubMed, Elsevier, and CNKI databases. The search terms were “astrocytes, scRNA-seq, heterogeneity, Alzheimer disease, spinal cord injury, multiple sclerosis” in Chinese and English. Finally, 74 articles were selected for viewing after screening according to inclusion criteria. RESULTS AND CONCLUSION: scRNA-seq studies related to the heterogeneity of astrocytes have shown that astrocyte is significantly heterogeneous across four aspects: species, developmental stage, central nervous system region, and pathological state. (1) Unique expression of certain genes occurs in astrocytes of different species, and the discovery of species-specific genes is beneficial for the translation of clinical studies. (2) During astrocyte development, differential gene expression emerged in the cellular subtypes identified at each stage, which further refined the cellular lineage of astrocytes and laid the foundation for the study of astrocyte developmental trajectories and mechanisms. (3) The discovery of differential gene expression allows regional localization of different astrocyte subpopulations and assists in the diagnosis and treatment of neurological diseases. (4) Astrocyte heterogeneity revealed by scRNA-seq can provide specific markers at the time of disease diagnosis and identify potential therapeutic targets. (5) The heterogeneity of astrocytes exists in many aspects, interacts with each other and is complex. The mechanisms of its generation, maintenance and transformation remain unclear. At present, molecular research on the single-cell level is still lacking. Linking transcriptionally defined astrocyte subpopulations to cellular activity, behavior and disease markers in real time remains one of the great challenges in the field. [ABSTRACT FROM AUTHOR]