颜林林 (2024-10-27 08:10):
#paper doi:10.1126/science.add7046, Science, 2023, Transcriptomic diversity of cell types across the adult human brain. 这篇文章来自瑞典卡罗琳斯卡学院(全球最顶尖的医学研究机构之一,负责颁发诺贝尔生理学或医学奖)和艾伦脑科学研究所(全球神经科学研究的重要中心之一,旨在通过大规模的脑科学研究和开放数据共享,推动对大脑结构和功能的理解)。该研究基于三位成人捐赠者的脑组织样本,采集了数百个不同脑区的样本,覆盖了包括端脑、中脑及脑干等部位,进行单核测序,得到超过三百万个细胞的表达数据,采用层次聚类和图分析技术对这些数据进行分析,将细胞划分为31个超簇及3000多个亚簇,并揭示了各簇在不同区域中的分布特点与功能关系,比较特别的是其中一个被命名为“溅射(Splatter)神经元”的超簇,因其复杂的分子特性和广泛分布,反映了神经元及其功能网络的高度异质性,成为本研究的重点之一。论文还阐明了皮层内兴奋性与抑制性神经元的层次性结构、不同脑区神经元的异质性、非神经元的星形胶质细胞的多样性和分布异质性等,从单细胞层面拓展了我们对基因表达与脑功能网络关系的理解。
Science, 2023-10-13. DOI: 10.1126/science.add7046
Transcriptomic diversity of cell types across the adult human brain
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Abstract:
The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins and revealing high diversity in midbrain and hindbrain neurons. Astrocytes and oligodendrocyte-lineage cells also exhibited regional diversity at multiple scales. The transcriptomic census of the entire human brain presented in this work provides a resource for understanding the molecular diversity of the human brain in health and disease.
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