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

人类胎儿小脑谱系发育和空间组织的单细胞多组学分析

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作者: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

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.

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