Transcriptome analyses of cortical projection neurons and interneurons via Tbr2(Eomes)-mediated transgenic lineage tracing

In the cerebral cortex, projection neurons and interneurons work coordinately to establish functional neural networks and to control the balance between excitatory versus inhibitory synaptic activities for normal cortical functions. While the specific mechanisms that control productions of projection neurons and interneurons are beginning to be revealed, a global characterization of the molecular differences between these two groups of neurons is in need for a more comprehensive understanding of their developmental specifications as well as their cortical functions. Previous studies have shown that the majority of cortical projection neurons are produced by radial glial cells (RGCs) through intermediate progenitor cells (IPCs) which can be marked by the expression of transcription factor Tbr2(Eomes). In this study, taking advantage of lineage tracing power of combining Tbr2(Eomes)-GFP and DCX-mRFP transgenic reporter mice, we prospectively separated IPC-derived neurons (IPNs) from non-IPC-derived neurons (non-IPNs) of the embryonic cortex. Molecular characterizations revealed that IPNs and non-IPNs were enriched with projection neurons and interneurons, respectively. Transcriptome analyses documented distinct groups of genes differentially expressed between these two groups of neurons. These data present a useful resource for further investigation of the molecular regulations and functions of projection neurons and interneurons. Transcriptome of two cortical neuron groups were analyzed在大脑皮层（cerebral cortex）中，投射神经元（projection neurons）与中间神经元（interneurons）协同作用，构建功能性神经网络，并调控兴奋性突触活动与抑制性突触活动之间的平衡，以维持皮层的正常功能。尽管目前调控投射神经元和中间神经元产生的特定机制已逐渐被揭示，但要更全面地理解这两类神经元的发育特性及其皮层功能，仍需对二者之间的分子差异进行全局性表征。既往研究表明，大多数皮层投射神经元由放射状胶质细胞（radial glial cells, RGCs）通过中间祖细胞（intermediate progenitor cells, IPCs）产生，而中间祖细胞可通过转录因子Tbr2(Eomes)的表达进行标记。本研究结合Tbr2(Eomes)-GFP与DCX-mRFP转基因报告小鼠（transgenic reporter mice）的谱系示踪（lineage tracing）技术，前瞻性地从胚胎皮层（embryonic cortex）中分离出了中间祖细胞来源神经元（IPC-derived neurons, IPNs）与非中间祖细胞来源神经元（non-IPC-derived neurons, non-IPNs）。分子表征结果显示，IPNs与non-IPNs分别富集了投射神经元与中间神经元。转录组分析（transcriptome analyses）表明，这两类神经元之间存在多组显著差异表达的基因（differentially expressed genes）。本研究数据为进一步探究投射神经元和中间神经元的分子调控机制与功能提供了宝贵的研究资源。本研究对两组皮层神经元的转录组进行了分析。