학술논문
Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations
Document Type
article
Author
Janne Koskimäki; Dongdong Zhang; Yan Li; Laleh Saadat; Thomas Moore; Rhonda Lightle; Sean P. Polster; Julián Carrión-Penagos; Seán B. Lyne; Hussein A. Zeineddine; Changbin Shi; Robert Shenkar; Sharbel Romanos; Kenneth Avner; Abhinav Srinath; Le Shen; Matthew R. Detter; Daniel Snellings; Ying Cao; Miguel A. Lopez-Ramirez; Gregory Fonseca; Alan T. Tang; Pieter Faber; Jorge Andrade; Mark Ginsberg; Mark L. Kahn; Douglas A. Marchuk; Romuald Girard; Issam A. Awad
Source
Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-15 (2019)
Subject
Language
English
ISSN
2051-5960
Abstract
Abstract Cerebral cavernous malformations (CCMs) are dilated capillaries causing epilepsy and stroke. Inheritance of a heterozygous mutation in CCM3/PDCD10 is responsible for the most aggressive familial form of the disease. Here we studied the differences and commonalities between the transcriptomes of microdissected lesional neurovascular units (NVUs) from acute and chronic in vivo Ccm3/Pdcd10 ECKO mice, and cultured brain microvascular endothelial cells (BMECs) Ccm3/Pdcd10 ECKO . We identified 2409 differentially expressed genes (DEGs) in acute and 2962 in chronic in vivo NVUs compared to microdissected brain capillaries, as well as 121 in in vitro BMECs with and without Ccm3/Pdcd10 loss (fold change ≥ |2.0|; p