Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Int J Mol Sci. 2022 Feb 17;23(4):2236. doi: 10.3390/ijms23042236.
Oligodendrocyte precursor cells (OPCs) serve as progenitor cells of terminally differentiated oligodendrocytes. Past studies have confirmed the importance of epigenetic system in OPC differentiation to oligodendrocytes. High mobility group A1 (HMGA1) is a small non-histone nuclear protein that binds DNA and modifies the chromatin conformational state. However, it is still completely unknown about the roles of HMGA1 in the process of OPC differentiation. In this study, we prepared primary OPC cultures from the neonatal rat cortex and examined whether the loss- and gain-of-function of HMGA1 would change the mRNA levels of oligodendrocyte markers, such as , , and during the process of OPC differentiation. In our system, the mRNA levels of , , and increased depending on the oligodendrocyte maturation step, but the level of mRNA decreased. When HMGA1 was knocked down by a siRNA approach, the mRNA levels of , , and were smaller in OPCs with siRNA compared to the ones in the control OPCs. On the contrary, when HMGA1 expression was increased by transfection of the plasmid, the mRNA levels of , , and were slightly larger compared to the ones in the control OPCs. These data may suggest that HMGA1 participates in the process of OPC differentiation by regulating the mRNA expression level of myelin-related genes.
少突胶质前体细胞 (OPC) 作为终末分化的少突胶质细胞的祖细胞。过去的研究已经证实了表观遗传系统在 OPC 向少突胶质细胞分化中的重要性。高迁移率族蛋白 A1 (HMGA1) 是一种小的非组蛋白核蛋白，可与 DNA 结合并改变染色质构象状态。然而，HMGA1 在 OPC 分化过程中的作用仍完全未知。在这项研究中，我们从新生大鼠皮层中制备了原代 OPC 培养物，并研究了 HMGA1 的缺失和功能获得是否会改变 OPC 分化过程中少突胶质细胞标志物的 mRNA 水平，如 、 、 和 。在我们的系统中， 、 、 和 的 mRNA 水平随着少突胶质细胞成熟阶段的增加而增加，但 mRNA 的水平降低。当使用 siRNA 方法敲低 HMGA1 时，与对照 OPC 相比，HMGA1 siRNA 的 OPC 中 、 、 和 的 mRNA 水平较小。相反，当通过转染 质粒增加 HMGA1 的表达时，与对照 OPC 相比， 、 、 和 的 mRNA 水平略有增加。这些数据可能表明 HMGA1 通过调节与髓鞘相关基因的 mRNA 表达水平参与 OPC 分化过程。
