Single-cell sequencing of glioblastoma reveals central nervous system susceptibility to SARS-CoV-2

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell. Methods: We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma. Results: The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs and NPCs, from clinical specimens. Conclusions: These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma. Four GBM tissue specimens and their adjacent brain tissues (as described in the metadata_readme.txt) Transcriptome and SampleTag information of single cells was obtained through BD Rhapsody System. Sample tag 01, 03, 05, 07 was GBM tissues and Sample tag 02, 04, 06, 08 was their adjacent brain tissues respectively. Single cells obtained from eight samples was loaded on two BD Cartridge. Sample tag 01-04 on Cartridge 106 and Sample tag 05-08 on Cartridge 108. Cartridge 106 got two package: * JZsc106*.fastq.gz and * JZsc107*.fastq.gz; while Cartridge 108 got two package: * JZsc108*.fastq.gz and * JZsc109*.fastq.gz. 106 and 108 are single-cell expression matrix. 107 and 109 are tag sequencing data (SampleTag library). Therefore, each sample records represent mixed tissue sample. Raw sequencing reads of cDNA library and SampleTag library were processed through the BD Rhapsody Whole Transcriptome Assay Analysis Pipeline. * R1.fastq.gz represents quality-filtered R1 reads and * R2.fastq.gz represents the quality-filtered R2 reads.