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灵长类端脑的区域特化和神经干细胞命运进展的分子程序。

Molecular programs of regional specification and neural stem cell fate progression in macaque telencephalon.

机构信息

Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA.

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.

出版信息

Science. 2023 Oct 13;382(6667):eadf3786. doi: 10.1126/science.adf3786.

Abstract

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primate-biased galanin-like peptide () signaling in the anteroventral telencephalon. Regional transcriptomic variations were observed along the frontotemporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression.

摘要

在大脑早期发育过程中,会发生区域模式形成和神经干细胞(NSC)命运特化等复杂过程。然而,我们对包括保守和物种特异性特征在内的灵长类动物这些过程的理解仍然有限。在这里,我们对来自食蟹猴大脑早期前脑的多个区域的 761,529 个单细胞转录组进行了分析。我们揭示了早期组织中心的分子程序及其与 NSCs 的相互作用,发现了在前脑腹侧隔区中具有灵长类偏向性的甘丙肽样肽(GALP)信号。在新皮质 NSC 进展的早期阶段以及神经元和星形胶质细胞中,沿额颞轴观察到区域转录组变化。此外,我们发现与神经精神疾病和脑癌风险相关的基因可能在早期大脑组织者和 NSC 进展过程中发挥关键作用。

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