【文献速递】小鼠大脑皮层细胞多样性的分子表征

文章信息

标题：Molocular logic of cellular diversification in the mouse cerebral cortex
期刊：nature
日期：June 23, 2021

The mammalian cerebral cortex has an unparalleled diversity of cell types, which are generated during development through a series of temporally orchestrated events thar are under tight ecolutionaary 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 unknown, largely due to the large number of cell classes that undergo gynamic cell-state transitions over extended developmental time lines.Here we generate a comprehensice atlas of the developmental time lines.Here we generate a comprehensive atlas of the develiping mouse ceocortex, using single-cell RNA sequencing and single-cell assay every day throughout embryonic corticogenesis and at early postnatal ages, and complemented the sequencing data with a spatial transcriptomics time course. We computationally reconstruct decelopmental trajectories across the dicersity of cortical cell classes, and inger their spatial organization and the gene regulatory programs that accompany theri lineage bifurcation decisions and differentiation trajectories. Finally we demonstrate how this developmental map pinpoints the orgin of lineage-specific developmental abnornalities that are linked to aberrant corticogenesis in mutant mice. The data procide a global picture of the regulatory mechanisms that govern cellular dicersification in the neocortex.

哺乳动物的大脑皮层具有无与伦比的细胞类型多样性，它们是在发育过程中通过一系列时间策划的事件产生的，这些事件在严格的进化约束下，对适当的皮层组装和功能至关重要。然而，控制皮质细胞类型的建立和组织的分子逻辑仍然是未知的，这在很大程度上是由于大量的细胞类群在延长的发育时间线上经历了动态的细胞状态转变。在这里，使用单细胞RNA测序和单细胞转座酶可访问染色质测序方法我们生成了一个正在发育的小鼠新皮层的综合图集。我们在胚胎皮生和产后早期每天采样新皮质，并通过空间转录组时间过程来补充测序数据。我们计算重建跨越皮质细胞类别多样性的发展轨迹，并推断它们的空间组织和基因调控程序，伴随它们的谱系分岔决定和分化轨迹。最后，我们展示了这张发展地图是如何确定与突变小鼠的异常相关物发生相关的谱系-特异性发展异常的起源，这些数据提供了一幅控制新皮层细胞多样化的调控机制的图景。