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Expression profiles of RNA‐Seq‐based grey matter‐specific genes versus white matter‐specific genes in grey matter lesions of multiple sclerosis
Author(s) -
Satoh Junichi,
Kino Yoshihiro
Publication year - 2015
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/cen3.12218
Subject(s) - grey matter , white matter , multiple sclerosis , biology , transcriptome , pathology , human brain , gene , gene expression , genetics , neuroscience , medicine , magnetic resonance imaging , immunology , radiology
Objectives Accumulating evidence shows that formation of cortical grey matter lesions, characterized by accumulation of activated microglia, axonal transection, synaptic loss and neuronal apoptosis, is common in multiple sclerosis ( MS ) beginning at the early stage. Grey matter lesions are closely associated with disease progression and permanent disability in MS . At present, the precise molecular signature characteristic of grey matter damage in MS brains remains to be intensively characterized. Methods To elucidate this, we identified grey matter‐specific genes ( GMSG ) and white matter‐specific genes ( WMSG ) abundantly expressed in the normal human brain by analyzing a RNA ‐Seq dataset numbered SRP 033291, composed of the comprehensive transcriptome of separated grey matter and white matter samples. Then, we studied expression profiles of GMSG and WMSG in MS lesions by analyzing microarray datasets derived from representative cases of grey matter lesions and white matter lesions. Results We identified 714 RNA ‐Seq‐based GMSG closely related to neuronal functions and 378 WMSG with relevance to glial functions. Numerous WMSG , such as KLK 6, GJB 1 and MYRF , were downregulated in both grey matter and white matter lesions, whereas the expression of various GMSG , such as PVALB , NEUROD 6 and LINGO 1, was reduced exclusively in grey matter lesions. Conclusions Grey matter lesions of MS are characterized by underexpression of grey matter components, and the panel of RNA ‐Seq‐based GMSG and WMSG serves as molecular markers for discrimination between grey matter and white matter lesions of MS .