Ischemic stroke-related gene expression profiles across species: a meta-analysis

Abstract

Stroke patients are often left with permanent disabilities with no regenerative treatment options. Unbiased RNA sequencing studies decoding the transcriptional signature of stroked tissue hold promise to identify new potential targets and pathways directed to improve treatment for stroke patients. Here, gene expression profiles of stroked tissue across different time points, species, and stroke models were compared using NCBI GEO database. In total, 34 datasets from mice, rats, humans, and primates were included, exploring gene expression differences in healthy and stroked brain tissue. Distinct changes in gene expression and pathway enrichment revealed the heterogenicity of the stroke pathology in stroke-related pathways e.g., inflammatory responses, vascular repair, remodelling and cell proliferation and adhesion but also in diverse general, stroke-unrelated pathways that have to be carefully considered when evaluating new promising therapeutic targets.

Keywords: Animal models; Gene expression; Gene ontology; Hypoxia; Ischemia; Meta analysis; Preclinical research; Stroke; Transcriptomics.

Fig. 1

Overview of studies dissecting stroke-related gene expression differences in the brain. (A) (left) Excluded and included stroke studies from NCBI GEO. (Right) Exclusion of datasets subdivided by species (mouse, rat, human and primates) with missing information, duplicates, pooled samples, poor quality controls, and no clear separation between stroked and non-stroked groups were further excluded. (B) Distribution of individual studies by time point, stroke model and sex. (C) Number of gene hits in individual studies. More information about the IDs can be found in Suppl Table 1. (D) Principal component analysis (PCA) of all stroke studies across different species and time points

Fig. 2

Gene expression profiles after stroke differ across species. (A) Venn Diagram representing number of shared and differentially expressed genes between mice and rats to different time points. (B) Gene ontology analysis of a subset of most significantly enriched biological processes in rats and mice. (C) Venn Diagram representing number of shared and differentially expressed genes between permanent MCAo and transient MCAo and the photothrombotic stroke model at different time points. (D) Gene ontology analysis of a subset of most significantly enriched biological processes in different stroke models. (E) Venn Diagram representing number of shared and differentially expressed genes between different time periods after stroke. (F) Gene ontology analysis of a subset of most significantly enriched biological processes at different time points