Single-cell multi-omics analysis of lineage development and spatial organization in the human fetal cerebellum.

IF 13 1区 生物学 Q1 CELL BIOLOGY
Fuqiang Yang, Ziqi Zhao, Dan Zhang, Yu Xiong, Xinran Dong, Yuchen Wang, Min Yang, Taotao Pan, Chuanyu Liu, Kaiyi Liu, Yifeng Lin, Yongjie Liu, Qiang Tu, Yashan Dang, Mingyang Xia, Da Mi, Wenhao Zhou, Zhiheng Xu
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Abstract

Human cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum.

Abstract Image

人类胎儿小脑发育和空间组织的单细胞多组学分析
人类小脑包含众多神经元,与大脑的发育模式截然不同。在这里,我们对孕周(GW)13至18的胎儿样本进行了scRNA-seq、scATAC-seq和空间转录组分析,以探索发育中的人类小脑出现的细胞多样性和发育程序。我们发现了跨物种保守的过渡性颗粒细胞祖细胞。我们对颗粒细胞和浦肯野细胞的特殊模式进行了多维剖析。我们发现 PARM1 在人类和小鼠颗粒细胞中的分布不一致。我们在菱形唇处发现了一个新的潜在神经上皮细胞群。我们还解析了浦肯野细胞和单极刷状细胞的各种亚型,并揭示了控制其多样化的基因调控网络。因此,我们的研究为人类胎儿小脑提供了一个宝贵的多组学图谱,并推进了我们对人类小脑发育和空间组织的理解。
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来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
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