Abstract:
:Temporal lobe epilepsy (TLE) is the most prevalent and often devastating form of epilepsy. The molecular mechanism underlying the development of TLE remains largely unclear, which hinders the discovery of effective antiepileptogenic drugs. Here we adopted a systems-level approach integrating transcriptomic profiles of three epileptogenesis stages to identify key regulators underlying epilepsy progression. Associating stage-specific gene meta-signatures with brain cell-specialized modules revealed positive regulation of glial migration and adhesion, cytokine production, and neuron death, and downregulation of synaptic transmission and ion transport during epileptogenesis. We identified 265 key regulators driving these processes and 72 of them were demonstrated associating with seizure frequency and/or hippocampal sclerosis in human TLE. Importantly, the upregulation of FAM107A, LAMB2, LTBP1 and TGIF1, which are mainly involved in nervous system development, were found contributing to both conditions. Our findings present the evolution landscape of epileptogenesis and provide candidate regulators that may serve as potential antiepileptogenic targets.
journal_name
Genomicsjournal_title
Genomicsauthors
Fu Y,Wu Z,Guo Z,Chen L,Ma Y,Wang Z,Xiao W,Wang Ydoi
10.1016/j.ygeno.2019.09.020subject
Has Abstractpub_date
2020-03-01 00:00:00pages
1768-1780issue
2eissn
0888-7543issn
1089-8646pii
S0888-7543(19)30405-7journal_volume
112pub_type
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