Abstract:
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 (RLSVZ) 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.
摘要:
我们对妊娠晚期人类胎儿小脑发育的理解,星形胶质细胞生成的关键时期,少突胶质细胞,和单极刷细胞(UBC),仍然有限。这里,我们对18-25孕周(GWs)的人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祖细胞分布在白质(WM)附近的菱形唇(RLSVZ)的室下区,形成层结构。我们还描绘了从星形放射状胶质细胞(ARG)到Bergmann胶质祖细胞(BGP)的两种轨迹,并将少突胶质细胞(ORG)识别为原始少突胶质细胞祖细胞(PriOPCs)的一种来源。此外,我们对21三体胎儿小脑在这一阶段的scRNA-seq分析揭示了细胞粘附途径和粘着斑途径等途径中异常上调的基因,这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。