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人类胎儿大脑中中间神经元的起源与分子多样性

Interneuron origin and molecular diversity in the human fetal brain.

作者信息

Yu Yuan, Zeng Zhiwei, Xie Danlin, Chen Renliang, Sha Yongqiang, Huang Shiying, Cai Wenjie, Chen Wanhua, Li Wenjun, Ke Rongqin, Sun Tao

机构信息

Center for Precision Medicine, Huaqiao University, Xiamen, Fujian, China.

Taokang Institute of Neuro Medicine, Xiamen, Fujian, China.

出版信息

Nat Neurosci. 2021 Dec;24(12):1745-1756. doi: 10.1038/s41593-021-00940-3. Epub 2021 Nov 4.

DOI:10.1038/s41593-021-00940-3
PMID:34737447
Abstract

Precise generation of excitatory neurons and inhibitory interneurons is crucial for proper formation and function of neural circuits in the mammalian brain. Because of the size and complexity of the human brain, it is a challenge to reveal the rich diversity of interneurons. To decipher origin and diversity of interneurons in the human fetal subpallium, here we show molecular features of diverse subtypes of interneuron progenitors and precursors by conducting single-cell RNA sequencing and in situ sequencing. Interneuron precursors in the medial and lateral ganglionic eminence simultaneously procure temporal and spatial identity through expressing a combination of specific sets of RNA transcripts. Acquisition of various interneuron subtypes in adult human brains occurs even at fetal stages. Our study uncovers complex molecular signatures of interneuron progenitors and precursors in the human fetal subpallium and highlights the logic and programs in the origin and lineage specification of various interneurons.

摘要

兴奋性神经元和抑制性中间神经元的精确生成对于哺乳动物大脑神经回路的正常形成和功能至关重要。由于人类大脑的大小和复杂性,揭示中间神经元丰富的多样性是一项挑战。为了解析人类胎儿大脑皮质下中间神经元的起源和多样性,我们在此通过进行单细胞RNA测序和原位测序展示了中间神经元祖细胞和前体细胞不同亚型的分子特征。内侧和外侧神经节隆起中的中间神经元前体细胞通过表达特定RNA转录本组合同时获得时间和空间身份。甚至在胎儿阶段,成人大脑中就已出现各种中间神经元亚型。我们的研究揭示了人类胎儿大脑皮质下中间神经元祖细胞和前体细胞复杂的分子特征,并突出了各种中间神经元起源和谱系特化中的逻辑和程序。

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