小柯机器人

研究揭示小鼠大脑皮层细胞多样化的分子逻辑
2021-06-27 15:53

美国哈佛大学Paola Arlotta、麻省理工学院Aviv Regev等研究人员合作揭示小鼠大脑皮层细胞多样化的分子逻辑。这一研究成果于2021年6月23日在线发表在国际学术期刊《自然》上。

研究人员使用单细胞RNA测序和单细胞转座酶可及染色质测序来生成了发育中的小鼠新皮层图谱。研究人员在整个胚胎皮层发生和出生后早期每天对新皮层进行采样,并用空间转录组学时间过程补充测序数据。研究人员通过计算重建了皮层细胞类别多样性的发育轨迹,并推断出它们空间组织和伴随其谱系分叉决策和分化轨迹的基因调控程序。最后,研究人员展示了该发育图如何确定与突变小鼠皮层发生异常相关的谱系特异性发育起源。这些数据提供了控制新皮层细胞多样化调节机制的全景图谱。

据悉,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在严格进化约束下的时间协调事件产生的,对于适当的皮层组装和功能至关重要。然而,支配皮层细胞类型建立和组织的分子逻辑仍然未知,这主要是由于大量细胞类别在延长的发育时间线上经历了动态细胞状态转换。

附:英文原文

Title: Molecular logic of cellular diversification in the mouse cerebral cortex

Author: Daniela J. Di Bella, Ehsan Habibi, Robert R. Stickels, Gabriele Scalia, Juliana Brown, Payman Yadollahpour, Sung Min Yang, Catherine Abbate, Tommasso Biancalani, Evan Z. Macosko, Fei Chen, Aviv Regev, Paola Arlotta

Issue&Volume: 2021-06-23

Abstract: 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 function1,2. 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 dynamic cell-state transitions over extended developmental timelines. Here we generate a comprehensive atlas of the developing mouse neocortex, using single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing. We sampled the neocortex every day throughout embryonic corticogenesis and at early postnatal ages, and complemented the sequencing data 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 that are linked to aberrant corticogenesis in mutant mice. The data provide a global picture of the regulatory mechanisms that govern cellular diversification in the neocortex.

DOI: 10.1038/s41586-021-03670-5

Source: https://www.nature.com/articles/s41586-021-03670-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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