Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Gene. 2014 May 1;540(2):191-200. doi: 10.1016/j.gene.2014.02.038. Epub 2014 Feb 26.
The olfactory system undergoes persistent regeneration throughout life. Olfactory ensheathing cells (OECs) are a specialized class of glia found exclusively in the olfactory system. OECs wrap olfactory sensory neuron axons and support their growth from the olfactory epithelium, and targeting to the olfactory bulb, during development and life-long regeneration. Because of this function and their ability to cross the boundary between central and peripheral nervous systems, OECs are attractive candidates for cell-based regenerative therapies to promote axonal repair in the injured nervous system. OECs are a molecularly, topologically and functionally heterogeneous group of cells and the mechanisms underlying the development and function of specific OEC subpopulations are poorly defined. This situation has affected the outcome and interpretation of OEC-based regenerative strategies. Here we show that the transcription factor Runx1 is selectively expressed in OECs of the inner olfactory nerve layer of the mouse olfactory bulb and in their precursors in the OEC migratory mass. Furthermore, we provide evidence that in vivo knockdown of mouse Runx1 increases the proliferation of the OECs in which Runx1 is expressed. Conversely, Runx1 overexpression in primary cultures of OECs reduces cell proliferation in vitro. Decreased Runx1 activity also leads to an increase in Runx1-expressing OEC precursors, with a parallel decrease in the number of more developmentally mature OECs. These results identify Runx1 as a useful new marker of a distinct OEC subpopulation and suggest that Runx1 is important for the development of this group of OECs. These observations provide an avenue for further exploration into the molecular mechanisms underlying the development and function of specific OEC subpopulations.
嗅觉系统在整个生命周期中都经历持续的再生。嗅鞘细胞（OEC）是一种专门的神经胶质细胞，仅存在于嗅觉系统中。在发育和终生再生过程中，OEC 包裹嗅感觉神经元轴突，并支持它们从嗅上皮向嗅球生长。由于这种功能及其穿过中枢和周围神经系统边界的能力，OEC 是基于细胞的再生治疗的有吸引力的候选物，可促进损伤的神经系统中的轴突修复。OEC 是一群分子上、拓扑结构上和功能上具有异质性的细胞，特定 OEC 亚群的发育和功能的机制尚未明确。这种情况影响了基于 OEC 的再生策略的结果和解释。在这里，我们表明转录因子 Runx1 选择性地表达在小鼠嗅球内嗅神经层的 OEC 及其在 OEC 迁移质中的前体细胞中。此外，我们提供证据表明，体内敲低小鼠 Runx1 可增加 Runx1 表达的 OEC 的增殖。相反，Runx1 在 OEC 原代培养物中的过表达可减少体外细胞增殖。Runx1 活性降低还会导致 Runx1 表达的 OEC 前体细胞增加，同时更发育成熟的 OEC 数量减少。这些结果将 Runx1 确定为一个独特的 OEC 亚群的有用的新标志物，并表明 Runx1 对这群 OEC 的发育很重要。这些观察结果为进一步探索特定 OEC 亚群的发育和功能的分子机制提供了途径。
