Different gene expression patterns between mouse and human brain pericytes revealed by single-cell/nucleus RNA sequencing

Aims

Pericytes in the brain play important roles for microvascular physiology and pathology and are affected in neurological disorders and neurodegenerative diseases. Mouse models are often utilized for pathophysiology studies of the role of pericytes in disease; however, the translatability is unclear as brain pericytes from mouse and human have not been systematically compared. In this study, we investigate the similarities and differences of brain pericyte gene expression between mouse and human. Our analysis provides a comprehensive resource for translational studies of brain pericytes.

Methods

We integrated and compared four mouse and human adult brain pericyte single-cell/nucleus RNA-sequencing datasets derived using two single-cell RNA sequencing platforms: Smart-seq and 10x. Gene expression abundance and specificity were analyzed. Pericyte-specific/enriched genes were assigned by comparison with endothelial cells present in the same datasets, and mouse and human pericyte transcriptomes were subsequently compared to identify species-specific genes.

Results

An overall concordance between pericyte transcriptomes was found in both Smart-seq and 10x data. 206 orthologous genes were consistently differentially expressed between human and mouse from both platforms, 91 genes were specific/up-regulated in human and 115 in mouse. Gene ontology analysis revealed differences in transporter categories in mouse and human brain pericytes. Importantly, several genes implicated in human disease were expressed in human but not in mouse brain pericytes, including SLC6A1, CACNA2D3, and SLC20A2.

Conclusions

This study provides a systematic illustration of the similarities and differences between mouse and human adult brain pericytes.