Spatial and cell type transcriptional landscape of human cerebellar development.

Spatial and cell type transcriptional landscape of human cerebellar development.
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DOI:
10.1038/s41593-021-00872-y
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发表时间:
2021-08
影响因子:
25
通讯作者:
Millen KJ
Millen KJ
中科院分区:
医学1区
文献类型:
--
作者:
Aldinger KA;Thomson Z;Phelps IG;Haldipur P;Deng M;Timms AE;Hirano M;Santpere G;Roco C;Rosenberg AB;Lorente-Galdos B;Gulden FO;O'Day D;Overman LM;Lisgo SN;Alexandre P;Sestan N;Doherty D;Dobyns WB;Seelig G;Glass IA;Millen KJ

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人类新生儿的小脑是其成年大小的四分之一,但包含了将环境线索与成年后发展的运动、认知和情感技能相结合所需的蓝图。虽然成熟的小脑神经解剖学研究得很好,但对其发育起源的了解有限。在这里,我们结合激光捕获显微镜和Split-Seq单核转录组学,系统地绘制了人胎小脑的分子、细胞和空间组成图。我们分析了不同细胞类型和不同发育阶段的不同功能区域和基因表达动态。由此得到的细胞图谱表明,小脑突起的分子组织概括了不同于小鼠小脑的细胞结构上不同的区域和发育瞬时细胞类型。通过将儿童和成人神经疾病的主要基因映射到我们的数据集,我们确定了潜在的疾病机制的相关细胞类型。这些数据为探索人类小脑发育和疾病的细胞学基础提供了资源。
The human neonatal cerebellum is a fourth of its adult size, yet contains the blueprint required to integrate environmental cues with developing motor, cognitive, and emotional skills into adulthood. Although mature cerebellar neuroanatomy is well studied, understanding its developmental origins is limited. Here, we systematically mapped the molecular, cellular, and spatial composition of human fetal cerebellum by combining laser capture microscopy and SPLiT-seq single-nucleus transcriptomics. We profiled functionally distinct regions and gene expression dynamics within cell types and across development. The resulting cell atlas demonstrates that the molecular organization of the cerebellar anlage recapitulates cytoarchitecturally distinct regions and developmentally transient cell types that are distinct from the mouse cerebellum. By mapping genes dominant for pediatric and adult neurological disorders onto our dataset, we identify relevant cell types underlying disease mechanisms. These data provide a resource for probing the cellular basis of human cerebellar development and disease.
基因集富集分析变得简单。
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