3. The Transcriptome Dynamics of Mouse Cerebrum Development via
New Generation Sequencing Technology And Evolution Research of
Bryopsis hypnoides Chloroplast via Shot-gun Sequencing
A Dissertation Submitted to the Degree Committee of
Institute of Genomics, Chinese Academy of Sciences
4. 目 录
By Wei Xu
Supervised by Professor Jun Yu and Professor Songnian Hu
April 2011
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19. Abstract
Abstract
Brain, which is also called cerebrum, consists of two hemispheres. It’s the senior
nervous center controlling movements, producing feelings and realizing higher-level
brain functions. The molecular mechanism and regulation mechanism of brain
development has not yet been fully expounded. In this study, to help assess the
expression changes of genes involved in postnatal brain development, we carried out
a comparative study on mouse brain transcriptomes at three crucially developmental
stages (infant stage, 1weeks old; juvenile stage, 4 weeks old; adult stage, 10 weeks
old) using the next-generation sequencing technology (SOLiD).
Using SOLiD, we sequenced the transcriptomes at three developmental stages
(RNA-seq), then aligned the obtained reads to the mouse genome and annotated genes
using the GenBank database on NCBI. We acquired 11,929,828, 16,614,876 and
15,111,661 uniquely-mapped reads from infant, juvenile, and adult cerebrum samples,
respectively. Of these uniquely-mapped reads, 33%-47% were mapped to exons,
28%-34% were mapped to introns, and the others were mapped to intergenic regions.
We identified 15,344, 16,048 and 15,775 expressed genes in the mouse cerebrum of
infancy, juvenile and adult, respectively.
We used RPKM value to normalize the gene expression abundance among the
three developmental stages. The gene expression profiles were clustered into two
groups, one contains infant and juvenile cerebrums, and the other contains adult
cerebrum only.
Through comparative analysis of gene expression profiles, we found 5,768
expressed genes changed significantly between infant and juvenile cerebrums, while
the number of that between juvenile and adult cerebrums was 6,787 . Compared to
infant cerebrum, 4,106 differentially expressed genes were up-regulated in juvenile
cerebrum, while compared to juvenile cerebrum, 5,623 differentially expressed genes
were down-regulated in juvenile cerebrum. This phenomenon suggests that the
abundance of cerebrum expressed genes during the three stages were up-regulated and
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20. 第一部分 基于第二代测序技术的生后小鼠大脑组织发育的转录组研究
then down-regulated. The gene expression was enhanced markedly during puberty
comparied to other stages. These differently expressed genes reflected a vast
repertoire of genes involved in energy metabolism, signal transduction, cell apoptosis,
and so on. Remarkably, these differentially expressed genes also includes a large
number of genes related to cancers and neurologic diseases, suggested these genes
may play a role in the postnatal development of mouse cerebrum.
In our research, we found 1,493 transcription factors(Tfs) which involved in the
development of mouse cerebrum, some of which are essential for cerebrum
development such as E2f family, Pax6, Six3, Rax, ISL-1. The function of most Tfs
during cerebrum development are still unclear. In addition, we found 254, 304, 382
Tfs with low expression abundance (RPKM<1) in the three samples, respectively,
including some important genes for the postnatal development of mouse cerebrum
(Neurog2 、 Pax6 、 Six3). These lowly expressed Tfs undetected by DNA microarray
before may help us understand the cerebrum transcriptome deeply.
We studied the correlation between introns and exons and identified 2,079,
2,520 and 4,061 genes have intronic regions showing significant exprssion in three
stages, respectively.
Our recearches indetated that 10,590 genes have alternative transcripts in the
three samples totally. Moreover, we found 23,266 transciptional loci in the intergenic
region in all, 70.8% of which were annotated to the UTR extenstion region(16,477) ,
20.7% of which were confirmed by EST, 0.9% of which were annotated as the known
ncRNA, and other 7.6% (1,767) were identified as new transciptional loci.
Keywords: Cerebrum development, Gene expression profile, SOLiD,
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