Unique Transcriptome Patterns of the White and Grey Matter Corroborate Structural and Functional Heterogeneity in the Human Frontal Lobe

被引:38
作者
Mills, James D. [1 ]
Kavanagh, Tomas [1 ]
Kim, Woojin S. [2 ,3 ]
Chen, Bei Jun [1 ]
Kawahara, Yoshihiro [4 ]
Halliday, Glenda M. [2 ,3 ]
Janitz, Michael [1 ]
机构
[1] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia
[2] Neurosci Res Australia, Sydney, NSW, Australia
[3] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia
[4] Natl Inst Agrobiol Sci, Agrogen Res Ctr, Bioinformat Res Unit, Tsukuba, Ibaraki, Japan
来源
PLOS ONE | 2013年 / 8卷 / 10期
基金
英国医学研究理事会;
关键词
RNA-SEQ; GENE; ALZHEIMERS; NEURONS; DISEASE; COMPLEX; TOPHAT; CORTEX; GALAXY; VOLUME;
D O I
10.1371/journal.pone.0078480
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The human frontal lobe has undergone accelerated evolution, leading to the development of unique human features such as language and self-reflection. Cortical grey matter and underlying white matter reflect distinct cellular compositions in the frontal lobe. Surprisingly little is known about the transcriptomal landscape of these distinct regions. Here, for the first time, we report a detailed transcriptomal profile of the frontal grey (GM) and white matter (WM) with resolution to alternatively spliced isoforms obtained using the RNA-Seq approach. We observed more vigorous transcriptome activity in GM compared to WM, presumably because of the presence of cellular bodies of neurons in the GM and RNA associated with the nucleus and perinuclear space. Among the top differentially expressed genes, we also identified a number of long intergenic non-coding RNAs (lincRNAs), specifically expressed in white matter, such as LINC00162. Furthermore, along with confirmation of expression of known markers for neurons and oligodendrocytes, we identified a number of genes and splicing isoforms that are exclusively expressed in GM or WM with examples of GABRB2 and PAK2 transcripts, respectively. Pathway analysis identified distinct physiological and biochemical processes specific to grey and white matter samples with a prevalence of synaptic processes in GM and myelination regulation and axonogenesis in the WM. Our study also revealed that expression of many genes, for example, the GPR123, is characterized by isoform switching, depending in which structure the gene is expressed. Our report clearly shows that GM and WM have perhaps surprisingly divergent transcriptome profiles, reflecting distinct roles in brain physiology. Further, this study provides the first reference data set for a normal human frontal lobe, which will be useful in comparative transcriptome studies of cerebral disorders, in particular, neurodegenerative diseases.
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页数:18
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