Our ‘Dataset of the Week’ series features publicly available omics datasets of scientific value, intending to promote data sharing and reuse.

This week’s dataset comprises of bulk RNA-seq data from the publication titled ‘Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium', published in Cell (Sep 2020).

SARS-CoV-2 is known to induce neurological complications in many patients, but its molecular mechanisms of pathogenesis in the central nervous system are poorly characterized owing to the lack of a viable model system. This paper utilized human induced pluripotent stem cells (hiPSC) and choroid plexus organoids to examine the susceptibility of brain cells to SARS-CoV-2 infection.

Key Findings of the Publication:

• hiPSC-derived neurons and astrocytes showed limited susceptibility to SARS-CoV-2 infection, whereas choroid plexus epithelial cells were highly susceptible.
• Bulk RNA sequencing analysis of choroid plexus organoids revealed high expression levels of ACE2, a cell surface receptor that aids SARS-CoV-2 entry. This could explain the tropism of this cell type to the virus.
• Numerous pro-inflammatory cytokines were upregulated, including CCL2, IL8 and IL18. This is indicative of immune cell recruitment.
• Increased expression of cell death related genes accompanied by downregulation of cell junction genes could result in tight junction damage between choroid plexus epithelial cells, ultimately leading to loss of blood-brain integrity. This would enable the virus to enter the central nervous system and induce neurological complications.

Significance of the Dataset:

This dataset contains bulk RNA-seq data derived from hiPSC-derived choroid plexus organoids infected with SARS-CoV-2 and corresponding controls. Transcriptomic data from this model system could help shed light on the mechanisms of viral entry into the central nervous system and associated brain dysfunction.

Experimental Design:

Brain organoids were treated with vehicle control or infected with 103, 104, or 105 focus forming units (FFU) of SARS-CoV-2 for 24 or 72 hours (3 biological replicates per group) and harvested for bulk RNA sequencing.

Useful Links:

• The dataset (GSE 150392): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157852
• The publication: https://www.sciencedirect.com/science/article/abs/pii/S193459092030463X
• The curated and analyzed report from the dataset: https://omixwiki.elucidata.io/493/gse157852/human-pluripotent-stem-cell-deri