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发育过程中人小脑空间和细胞类型的转录概况获揭示
2021-06-20 16:29

美国西雅图儿童研究所Kathleen J. Millen、Kimberly A. Aldinger及其研究团队揭示了人小脑发育过程中空间和细胞类型的转录概况。该研究于2021年6月17日发表于国际学术期刊《自然-神经科学》杂志。

在本研究中,通过组合激光捕获显微镜和SPLiT-seq 单核转录组,研究人员系统地绘制了人胎儿小脑的分子、细胞和空间组成。研究人员对细胞类型和跨发育过程中的不同功能区域和基因表达动态进行了描绘。所得细胞图集证明小脑培基的分子组成可概括与小鼠小脑中不同的区域和发育过程中的瞬时细胞类型。通过将小儿和成人神经紊乱的主要基因映射到该数据集中,研究人员阐明了相关细胞类型的致病机制。这些数据为探测人体小脑发育和疾病细胞类型提供了资源。 

据悉,新生儿小脑是其成人小脑大小的四分之一,具有成年期所需的将环境信息与发育动力、认知和情感技巧整合的能力。虽然对成年小脑神经肿瘤进行了很好的研究,但对其发育起源的理解十分有限。

附:英文原文

Title: Spatial and cell type transcriptional landscape of human cerebellar development

Author: Kimberly A. Aldinger, Zachary Thomson, Ian G. Phelps, Parthiv Haldipur, Mei Deng, Andrew E. Timms, Matthew Hirano, Gabriel Santpere, Charles Roco, Alexander B. Rosenberg, Belen Lorente-Galdos, Forrest O. Gulden, Diana ODay, Lynne M. Overman, Steven N. Lisgo, Paula Alexandre, Nenad Sestan, Dan Doherty, William B. Dobyns, Georg Seelig, Ian A. Glass, Kathleen J. Millen

Issue&Volume: 2021-06-17

Abstract: The human neonatal cerebellum is one-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 of its developmental origins is limited. In this study, 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. SPLiT-seq single-nucleus RNA sequencing of the developing human cerebellum reveals cell-type complexities and prolonged maturation compared to mouse with important disease implications.

DOI: 10.1038/s41593-021-00872-y

Source: https://www.nature.com/articles/s41593-021-00872-y

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

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