Molecular logic of cellular diversification in the mouse cerebral cortex.
Molecular logic of cellular diversification in the mouse cerebral cortex.
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DOI：
10.1038/s41586-021-03670-5
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发表时间：
2021-07
期刊：
影响因子：
64.8
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中科院分区：
文献类型：
--
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哺乳动物大脑皮层具有无与伦比的细胞类型多样性，这些细胞类型是在发育过程中通过一系列时间上精心安排的事件产生的，这些事件受到严格的进化限制，对于正常的皮质组装和功能至关重要。然而，支配皮质细胞类型建立和组织的分子逻辑仍然难以捉摸，这主要是因为在延长的发育时间线上，大量的细胞类别经历了动态的细胞状态转换。在这里，我们已经生成了发育中的小鼠新皮质的全面的单细胞RNA-seq和单细胞atac-seq图谱，在整个胚胎皮质发生过程中和出生后早期每天都进行采样，并辅之以空间转录切割时间进程。我们通过计算重建不同皮质细胞类别的发育轨迹，并推断它们的空间组织以及伴随着它们的谱系分歧决定和分化轨迹的基因调控程序。最后，我们展示了这张发育图如何准确地指出了与突变动物异常皮质生成有关的谱系特异性发育异常的起源。这些数据提供了管理大脑皮层细胞多样化的调控机制的全球图景。
The mammalian cerebral cortex has an unparalleled diversity of cell types, which are generated during development through a series of temporally orchestrated events that are under tight evolutionary constraint and are critical for proper cortical assembly and function. However, the molecular logic that governs the establishment and organization of cortical cell types remains elusive, largely due to the large number of cell classes undergoing dynamic cell-state transitions over extended developmental timelines. Here, we have generated a comprehensive single-cell RNA-seq and single-cell ATAC-seq atlas of the developing mouse neocortex, sampled every day throughout embryonic corticogenesis and at early postnatal ages, complemented with a spatial transcriptomics time-course. We computationally reconstruct developmental trajectories across the diversity of cortical cell classes, and infer their spatial organization and the gene regulatory programs that accompany their lineage bifurcation decisions and differentiation trajectories. Finally, we demonstrate how this developmental map pinpoints the origin of lineage-specific developmental abnormalities linked to aberrant corticogenesis in mutant animals. The data provides a global picture of the regulatory mechanisms governing cellular diversification in the neocortex.
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