Yang Fuqiang, Zhao Ziqi, Zhang Dan, Xiong Yu, Dong Xinran, Wang Yuchen, Yang Min, Pan Taotao, Liu Chuanyu, Liu Kaiyi, Lin Yifeng, Liu Yongjie, Tu Qiang, Dang Yashan, Xia Mingyang, Mi Da, Zhou Wenhao, Xu Zhiheng
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Cell Discov. 2024 Feb 26;10(1):22. doi: 10.1038/s41421-024-00656-1.
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.
人类小脑包含众多神经元，呈现出与大脑截然不同的发育模式。在此，我们对妊娠第13至18周胎儿样本进行了单细胞RNA测序（scRNA-seq）、单细胞染色质可及性测序（scATAC-seq）和空间转录组分析，以探索发育中的人类小脑中细胞多样性和发育程序的出现。我们鉴定出了跨物种保守的过渡性颗粒细胞祖细胞。从多个维度剖析了颗粒细胞和浦肯野细胞中的特殊模式。对小脑叶的物种特异性基因表达模式进行了表征，我们发现PARM1在人类和小鼠颗粒细胞中的分布不一致。在菱唇处鉴定出了一个新的潜在神经上皮细胞簇。我们还解析了浦肯野细胞和单极刷状细胞的各种亚型，并揭示了控制它们分化的基因调控网络。因此，我们的研究提供了一份有价值的人类胎儿小脑多组学图谱，并增进了我们对人类小脑发育和空间组织的理解。
