Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis
Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis
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DOI：
10.1242/dev.022616
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发表时间：
2008-09-15
期刊：
影响因子：
4.6
通讯作者：
Matsuzaki, Fumio
中科院分区：
文献类型：
--
作者：
Kawaguchi, Ayano;Ikawa, Tomoko;Matsuzaki, Fumio
大脑细胞的多样性很大程度上归因于祖细胞的时空异质性。在哺乳动物的大脑发育中，由于神经祖细胞的核位置和基因表达的动态变化，很难确定它们的异质性。为了解决这一问题，我们系统地分析了小鼠胚胎中期大量单个祖细胞的cDNA谱。通过聚类分析和原位杂交，我们发现了一组区分根尖祖细胞和基部祖细胞的基因。尽管顶端祖细胞的全局基因表达谱相对均匀，但Notch信号成分的表达模式却高度可变，这可能导致了这些细胞的异质分裂模式。此外，我们成功地捕获了基底祖细胞的新生状态。这些细胞在出生后不久由顶端祖细胞分裂产生，并表现出主要Notch配体δ样1的强烈表达，随着细胞向心室区迁移，这种表达很快消失。我们还证明Notch信号的衰减会立即诱导顶端祖细胞分化为新生的基部祖细胞。因此，一个依赖于notch的反馈回路很可能在运作中，以维持两个祖种群。
Cellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development, it has been difficult to determine how heterogeneous the neural progenitor cells are, owing to dynamic changes in their nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage in mouse. By cluster analysis and in situ hybridization, we have identified a set of genes that distinguishes between the apical and basal progenitors. Despite their relatively homogeneous global gene expression profiles, the apical progenitors exhibit highly variable expression patterns of Notch signaling components, raising the possibility that this causes the heterogeneous division patterns of these cells. Furthermore, we successfully captured the nascent state of basal progenitor cells. These cells are generated shortly after birth from the division of the apical progenitors, and show strong expression of the major Notch ligand delta-like 1, which soon fades away as the cells migrate in the ventricular zone. We also demonstrated that attenuation of Notch signals immediately induces differentiation of apical progenitors into nascent basal progenitors. Thus, a Notch-dependent feedback loop is likely to be in operation to maintain both progenitor populations.