Zechel Sabrina, Zajac Pawel, Lönnerberg Peter, Ibáñez Carlos F, Linnarsson Sten
Department of Neuroscience, Karolinska Institute, Stockholm SE-171 77, Sweden.
Genome Biol. 2014;15(10):486. doi: 10.1186/s13059-014-0486-z.
Cortical interneurons originating from the medial ganglionic eminence, MGE, are among the most diverse cells within the CNS. Different pools of proliferating progenitor cells are thought to exist in the ventricular zone of the MGE, but whether the underlying subventricular and mantle regions of the MGE are spatially patterned has not yet been addressed. Here, we combined laser-capture microdissection and multiplex RNA-sequencing to map the transcriptome of MGE cells at a spatial resolution of 50 μm.
Distinct groups of progenitor cells showing different stages of interneuron maturation are identified and topographically mapped based on their genome-wide transcriptional pattern. Although proliferating potential decreased rather abruptly outside the ventricular zone, a ventro-lateral gradient of increasing migratory capacity was identified, revealing heterogeneous cell populations within this neurogenic structure.
We demonstrate that spatially resolved RNA-seq is ideally suited for high resolution topographical mapping of genome-wide gene expression in heterogeneous anatomical structures such as the mammalian central nervous system.
起源于内侧神经节隆起（MGE）的皮质中间神经元是中枢神经系统中最多样化的细胞之一。人们认为在MGE的脑室区存在不同的增殖祖细胞群，但MGE潜在的室下区和套层区域是否存在空间模式尚未得到研究。在此，我们结合激光捕获显微切割和多重RNA测序，以50μm的空间分辨率绘制MGE细胞的转录组图谱。
基于全基因组转录模式，鉴定出显示中间神经元成熟不同阶段的不同祖细胞群，并对其进行了拓扑映射。尽管增殖潜能在脑室区外相当突然地降低，但我们确定了迁移能力增加的腹侧梯度，揭示了这个神经发生结构内的异质性细胞群。
我们证明，空间分辨RNA测序非常适合对哺乳动物中枢神经系统等异质解剖结构中的全基因组基因表达进行高分辨率拓扑映射。
