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Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes.

Publication ,  Journal Article
Koskimäki, J; Girard, R; Li, Y; Saadat, L; Zeineddine, HA; Lightle, R; Moore, T; Lyne, S; Avner, K; Shenkar, R; Cao, Y; Shi, C; Polster, SP ...
Published in: JCI Insight
February 7, 2019

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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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

February 7, 2019

Volume

4

Issue

3

Location

United States

Related Subject Headings

  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Koskimäki, J., Girard, R., Li, Y., Saadat, L., Zeineddine, H. A., Lightle, R., … Awad, I. A. (2019). Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes. JCI Insight, 4(3). https://doi.org/10.1172/jci.insight.126167
Koskimäki, Janne, Romuald Girard, Yan Li, Laleh Saadat, Hussein A. Zeineddine, Rhonda Lightle, Thomas Moore, et al. “Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes.JCI Insight 4, no. 3 (February 7, 2019). https://doi.org/10.1172/jci.insight.126167.
Koskimäki J, Girard R, Li Y, Saadat L, Zeineddine HA, Lightle R, et al. Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes. JCI Insight. 2019 Feb 7;4(3).
Koskimäki, Janne, et al. “Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes.JCI Insight, vol. 4, no. 3, Feb. 2019. Pubmed, doi:10.1172/jci.insight.126167.
Koskimäki J, Girard R, Li Y, Saadat L, Zeineddine HA, Lightle R, Moore T, Lyne S, Avner K, Shenkar R, Cao Y, Shi C, Polster SP, Zhang D, Carrión-Penagos J, Romanos S, Fonseca G, Lopez-Ramirez MA, Chapman EM, Popiel E, Tang AT, Akers A, Faber P, Andrade J, Ginsberg M, Derry WB, Kahn ML, Marchuk DA, Awad IA. Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes. JCI Insight. 2019 Feb 7;4(3).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

February 7, 2019

Volume

4

Issue

3

Location

United States

Related Subject Headings

  • 42 Health sciences
  • 32 Biomedical and clinical sciences