Karolinska Institute, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden.
University of Helsinki, Research Program of Molecular Neurology and Folkhälsan Institute of Genetics, FI-00290 Helsinki, Finland.
J Cell Sci. 2020 Nov 9;133(21):jcs249789. doi: 10.1242/jcs.249789.
Many human cell types are ciliated, including neural progenitors and differentiated neurons. Ciliopathies are characterized by defective cilia and comprise various disease states, including brain phenotypes, where the underlying biological pathways are largely unknown. Our understanding of neuronal cilia is rudimentary, and an easy-to-maintain, ciliated human neuronal cell model is absent. The Lund human mesencephalic (LUHMES) cell line is a ciliated neuronal cell line derived from human fetal mesencephalon. LUHMES cells can easily be maintained and differentiated into mature, functional neurons within one week. They have a single primary cilium as proliferating progenitor cells and as postmitotic, differentiating neurons. These developmental stages are completely separable within one day of culture condition change. The sonic hedgehog (SHH) signaling pathway is active in differentiating LUHMES neurons. RNA-sequencing timecourse analyses reveal molecular pathways and gene-regulatory networks critical for ciliogenesis and axon outgrowth at the interface between progenitor cell proliferation, polarization and neuronal differentiation. Gene expression dynamics of cultured LUHMES neurons faithfully mimic the corresponding dynamics of human fetal midbrain. In LUHMES cells, neuronal cilia biology can be investigated from proliferation through differentiation to mature neurons.
许多人类细胞类型都有纤毛，包括神经祖细胞和分化神经元。纤毛病的特征是纤毛缺陷，包括各种疾病状态，包括大脑表型，其潜在的生物学途径在很大程度上尚不清楚。我们对神经元纤毛的了解还很初步，而且缺乏易于维持的有纤毛的人类神经元细胞模型。Lund 人类中脑（LUHMES）细胞系是一种源自人胎脑中脑的有纤毛神经元细胞系。LUHMES 细胞很容易维持，并在一周内分化为成熟的、有功能的神经元。它们作为增殖祖细胞和有丝分裂后、分化的神经元具有单个初级纤毛。在培养条件改变的一天内，这些发育阶段是完全可分离的。声 hedgehog（SHH）信号通路在分化的 LUHMES 神经元中活跃。RNA-seq 时间过程分析揭示了对于纤毛发生和轴突生长至关重要的分子途径和基因调控网络，这些过程发生在祖细胞增殖、极化和神经元分化的界面处。培养的 LUHMES 神经元的基因表达动态忠实地模拟了人胎脑中脑的相应动态。在 LUHMES 细胞中，可以从增殖到分化到成熟神经元来研究神经元纤毛生物学。
