Ramos Alexander D, Andersen Rebecca E, Liu Siyuan John, Nowakowski Tomasz Jan, Hong Sung Jun, Gertz Caitlyn, Salinas Ryan D, Zarabi Hosniya, Kriegstein Arnold R, Lim Daniel A
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Stem Cell. 2015 Apr 2;16(4):439-447. doi: 10.1016/j.stem.2015.02.007. Epub 2015 Mar 19.
While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations.
虽然已经鉴定出数千种长链非编码RNA（lncRNA），但已知控制神经干细胞（NSC）行为的lncRNA却很少。在这里，我们鉴定出Pinky（Pnky）是一种神经特异性lncRNA，它在胚胎期和出生后脑内调节神经干细胞的神经发生。在出生后的神经干细胞中，敲低Pnky可增强神经元谱系定向分化，并扩大过渡放大细胞群体，使神经元生成增加数倍。Pnky在进化上保守，且在发育中的人类大脑神经干细胞中表达。在胚胎小鼠皮层中，敲低Pnky可增加神经元分化并耗尽神经干细胞群体。Pnky与剪接调节因子PTBP1相互作用，敲低PTBP1也可增强神经发生。在神经干细胞中，Pnky和PTBP1调节一组与细胞表型相关的核心转录本的表达和可变剪接。因此，这些数据揭示Pnky是一种保守的lncRNA，它与关键的RNA加工因子相互作用，并调节胚胎期和出生后神经干细胞群体的神经发生。
