AI Article Synopsis
- The study aimed to find important genes and functions related to cerebral cavernous malformation (CCM) by analyzing RNA from different species and types of the disease.
- Researchers looked at RNA from human CCM samples, mouse cells, and tiny worms to identify different genes that were active or inactive in these models.
- They found common genes and functions that are important for understanding how CCM works, which could help in future research to develop treatments.
Article Abstract
The purpose of this study was to determine important genes, functions, and networks contributing to the pathobiology of cerebral cavernous malformation (CCM) from transcriptomic analyses across 3 species and 2 disease genotypes. Sequencing of RNA from laser microdissected neurovascular units of 5 human surgically resected CCM lesions, mouse brain microvascular endothelial cells, Caenorhabditis elegans with induced Ccm gene loss, and their respective controls provided differentially expressed genes (DEGs). DEGs from mouse and C. elegans were annotated into human homologous genes. Cross-comparisons of DEGs between species and genotypes, as well as network and gene ontology (GO) enrichment analyses, were performed. Among hundreds of DEGs identified in each model, common genes and 1 GO term (GO:0051656, establishment of organelle localization) were commonly identified across the different species and genotypes. In addition, 24 GO functions were present in 4 of 5 models and were related to cell-to-cell adhesion, neutrophil-mediated immunity, ion transmembrane transporter activity, and responses to oxidative stress. We have provided a comprehensive transcriptome library of CCM disease across species and for the first time to our knowledge in Ccm1/Krit1 versus Ccm3/Pdcd10 genotypes. We have provided examples of how results can be used in hypothesis generation or mechanistic confirmatory studies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413775 | PMC |
| http://dx.doi.org/10.1172/jci.insight.126167 | DOI Listing |
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