高度保守的环状 RNA 可维持哺乳动物大脑神经细胞处于祖细胞状态。
A Highly Conserved Circular RNA Is Required to Keep Neural Cells in a Progenitor State in the Mammalian Brain.
机构信息
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine within the Helmholtz Association, Systems Biology of Gene Regulatory Elements, Hannoversche Straße 28, 10115 Berlin, Germany.
CRTD-Center for Regenerative Therapies Dresden, TU Dresden, Fetscherstraße 105, 01307 Dresden, Germany.
出版信息
Cell Rep. 2020 Feb 18;30(7):2170-2179.e5. doi: 10.1016/j.celrep.2020.01.083.
circSLC45A4 is the main RNA splice isoform produced from its genetic locus and one of the highest expressed circRNAs in the developing human frontal cortex. Knockdown of this highly conserved circRNA in a human neuroblastoma cell line is sufficient to induce spontaneous neuronal differentiation, measurable by increased expression of neuronal marker genes. Depletion of circSlc45a4 in the developing mouse cortex causes a significant reduction of the basal progenitor pool and increases the expression of neurogenic regulators. Furthermore, knockdown of circSlc45a4a induces a significant depletion of cells in the cortical plate. In addition, deconvolution of the bulk RNA-seq data with the help of single-cell RNA-seq data validates the depletion of basal progenitors and reveals an increase in Cajal-Retzius cells. In summary, we present a detailed study of a highly conserved circular RNA that is necessary to maintain the pool of neural progenitors in vitro and in vivo.
circSLC45A4 是从其遗传基因座产生的主要 RNA 剪接异构体，也是发育中的人类额皮质中表达最高的 circRNA 之一。在人类神经母细胞瘤细胞系中敲低这种高度保守的 circRNA，足以诱导自发的神经元分化，可通过神经元标记基因的表达增加来衡量。在发育中的小鼠皮质中耗尽 circSlc45a4 会导致基础祖细胞池显著减少，并增加神经发生调节剂的表达。此外，敲低 circSlc45a4a 会导致皮质板中的细胞大量耗竭。此外，借助单细胞 RNA-seq 数据对批量 RNA-seq 数据进行反卷积验证了基础祖细胞的耗竭，并揭示了 Cajal-Retzius 细胞的增加。总之，我们对一种高度保守的环状 RNA 进行了详细研究，该 RNA 在维持体外和体内神经祖细胞库中是必需的。
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