Department of Molecular Biology, Graduate School of Biomedical Sciences, Rowan University, Stratford, New Jersey, USA; and.
School of Natural Sciences and Mathematics, Stockton University, Galloway, New Jersey, USA.
FASEB J. 2019 Mar;33(3):3291-3303. doi: 10.1096/fj.201801118R. Epub 2018 Nov 13.
The RNA-binding protein LIN28 is known to regulate cell fate, tissue growth, and pluripotency; however, a unified understanding of its role at the cellular level has not been achieved. Here, we address its developmental activity in mammalian postnatal neurogenesis. Constitutive expression of LIN28 in progenitor cells of the mouse subventricular zone (SVZ) caused several distinct effects: 1) the number of differentiated neurons in the olfactory bulb was dramatically reduced, whereas the relative abundance of 2 neuronal subtypes was significantly altered, 2) the population of proliferating neural progenitors in the SVZ was reduced, whereas the proportion of neuroblasts was increased, and 3) the number of astrocytes was reduced, occasionally causing them to appear early. Thus, LIN28 acts at a poststem cell/predifferentiation step, and its continuous expression caused a precocious phenotype unlike in other experimental systems. Furthermore, for the first time in a vertebrate system, we separate the majority of the biologic role of LIN28 from its known activity of blocking the microRNA let-7 by using a circular RNA sponge. We find that although LIN28 has a multifaceted role in the number and types of cells produced during postnatal neurogenesis, it appears that its action through let-7 is responsible for only a fraction of these effects.-Romer-Seibert, J. S., Hartman, N. W., Moss, E. G. The RNA-binding protein LIN28 controls progenitor and neuronal cell fate during postnatal neurogenesis.
RNA 结合蛋白 LIN28 已知调节细胞命运、组织生长和多能性；然而，其在细胞水平上的统一作用尚未得到实现。在这里，我们研究了它在哺乳动物出生后神经发生中的发育活性。LIN28 在小鼠侧脑室下区（SVZ）祖细胞中的组成型表达导致了几种不同的影响：1）嗅球中的分化神经元数量显著减少，而 2 种神经元亚型的相对丰度显著改变，2）SVZ 中的增殖神经祖细胞数量减少，而神经母细胞的比例增加，3）星形胶质细胞的数量减少，偶尔会导致它们过早出现。因此，LIN28 在干细胞/前分化阶段起作用，其持续表达导致了与其他实验系统不同的早熟表型。此外，我们首次在脊椎动物系统中，通过使用环状 RNA 海绵将 LIN28 的大部分生物学作用与其阻断 microRNA let-7 的已知活性分开。我们发现，尽管 LIN28 在出生后神经发生过程中产生的细胞数量和类型中具有多方面的作用，但它通过 let-7 的作用似乎只负责这些作用的一部分。-Romer-Seibert，J. S.，Hartman，N. W.，Moss，E. G. RNA 结合蛋白 LIN28 在出生后神经发生过程中控制祖细胞和神经元细胞命运。
