Transcriptome profile of pyramidal neuron from mouse cerebral cortex during induced plasticity

Neural plasticity is a general property of the brain to establish and consolidate new synaptic connections which is lost during adulthood. However, some of the histone deacetylase (HDAC) inhibitors (HDACi) have been found to reactivate plasticity in adult mice. We have exploited this to study the transcriptomics during induced plasticity by analyzing single type of neurons (pyramidal/Glutaminergic neurons) which is known to be actively involved in plasticity. With our recently developed nanoCAGE and CAGEscan method, we prepared pyramidal neurons transcriptome libraries from small amount of total RNA (30-100ng) and sequenced them with Illumina Genome Analizer IIx that yielded ~8 million(M) tags/library/condition on average. We have identified >9 M transcription starting sites with the mapped tags. We have also produced a good resource of paired end tags (>60 M). We have identified genes with their genome ontology terms which are involved in plasticity. Also, we have anticipated the involvement of non-protein coding RNAs including repeat elements and transcription factor networks. The results of this study might be used in the future to modulate the brain plasticity, for instance by generating targets for new drugs.

神经可塑性(Neural plasticity)是大脑建立并巩固新突触连接的通用生物学特性，该特性在成年时期会丧失。然而，部分组蛋白去乙酰化酶(histone deacetylase, HDAC)抑制剂(HDACi)已被发现可在成年小鼠体内重新激活神经可塑性。本研究利用这一现象，通过分析已知可主动参与可塑性过程的单一类型神经元——锥体神经元/谷氨酰胺能神经元(pyramidal/Glutaminergic neurons)，探究诱导可塑性过程中的转录组学特征。依托本研究新近开发的nanoCAGE与CAGEscan技术，我们从微量总RNA（30~100ng）中制备了锥体神经元的转录组文库，并使用Illumina Genome Analizer IIx进行测序，每个文库/实验条件平均可获得约800万条标签。通过比对得到的标签序列，我们已鉴定出超过900万个转录起始位点(transcription starting sites)。此外，我们还构建了包含超过6000万条双端标签的优质数据集资源。我们还鉴定出了一批携带基因本体论(Gene Ontology, GO)注释信息且参与神经可塑性过程的基因，同时预测了包括重复序列元件在内的非编码RNA(non-protein coding RNAs)以及转录因子网络在该过程中的潜在调控作用。本研究的成果未来可用于调控大脑神经可塑性，例如为新型药物开发筛选潜在作用靶点。