Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
Biomedical Pioneering Innovation Center, Department of Obstetrics and Gynecology, Academy for Advanced Interdisciplinary Studies, Third Hospital, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Changping Laboratory, Changping Laboratory, Yard 28, Science Park Road, Changping District, Beijing 102206, China.
Cell Rep. 2024 Aug 27;43(8):114586. doi: 10.1016/j.celrep.2024.114586. Epub 2024 Aug 12.
Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18-25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RL) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.
我们对于人类胎儿小脑在妊娠 2 个月末（这一时期对于星形胶质细胞、少突胶质细胞和单极刷状细胞（UBC）的产生至关重要）的发育的理解仍然有限。在此，我们对来自妊娠 18-25 周的人类胎儿小脑样本进行了单细胞 RNA 测序（scRNA-seq）。我们发现，增殖的 UBC 祖细胞分布在靠近白质（WM）的菱形唇（RL）的室下区，形成一层结构。我们还描绘了两条从星形胶质细胞起源的放射状胶质（ARGs）到伯格曼胶质祖细胞（BGPs）的轨迹，并将少突胶质细胞起源的放射状胶质（ORGs）视为原始少突胶质前体细胞（PriOPCs）的一个来源。此外，我们对该阶段唐氏综合征胎儿小脑的 scRNA-seq 分析揭示了细胞黏附途径和黏着斑途径等途径中异常上调的基因，这些基因可能促进神经元分化。总的来说，我们的研究为人类胎儿小脑的正常和异常发育提供了有价值的见解。
