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Overexpression of neural miRNAs miR‐9/9* and miR‐124 suppresses differentiation to Müller glia and promotes differentiation to neurons in mouse retina in vivo
Genes to Cells ( IF 1.3 ) Pub Date : 2020-09-26 , DOI: 10.1111/gtc.12809
Fumiko Suzuki 1 , Mariko Okuno 1 , Tomoya Tanaka 1 , Rikako Sanuki 1
Affiliation  

MicroRNAs (miRNAs) are known to regulate gene expression and modulate cellular differentiation. MicroRNA‐9/9* (miR‐9/9*) and microRNA‐124 (miR‐124) are highly expressed in the central nervous system. In vivo function of miR‐9/9* and miR‐124 has been investigated in detail, whereas there remain some discrepancies regarding neural development. To this end, we electroporated miR‐9/9*, miR‐124 or miR‐9/9*/124 expression plasmids into neonatal retinal progenitor cells (RPCs) in vivo and analyzed the fate of electroporated cells. Both miR‐9/9* and miR‐124 reduced the number of SOX9‐ and GS‐positive cells and increased that of TUBB3‐positive cells in the postnatal day 14 retina. No major effects on the proliferation and apoptosis of the electroporated cells were detected at least postnatal day 3. These indicated that miR‐9/9* and miR‐124 influence the cell fate of glial cells, thereby inducing their differentiation into neurons. Moreover, we found this cell fate modulation was occurred in RPCs indicating high‐level expression of miRNA, but not in the low level. Our results strongly suggest that high‐level miRNA overexpression is essential for directing cell fate by miR‐9/9* and miR‐124 interference.

中文翻译:

神经miRNA miR-9 / 9 *和miR-124的过表达在体内抑制小鼠Müller胶质细胞的分化并促进向神经元的分化

已知MicroRNA(miRNA)可以调节基因表达并调节细胞分化。MicroRNA-9 / 9 *(miR-9 / 9 *)和microRNA-124(miR-124)在中枢神经系统中高度表达。已对miR-9 / 9 *和miR-124的体内功能进行了详细研究,但在神经发育方面仍存在一些差异。为此,我们在体内将miR‐9 / 9 *,miR‐124或miR‐9 / 9 * / 124表达质粒电穿孔入了新生儿视网膜祖细胞(RPC),并分析了电穿孔细胞的命运。在出生后第14天的视网膜中,miR-9 / 9 *和miR-124均减少了SOX9和GS阳性细胞的数量,并增加了TUBB3阳性细胞的数量。至少在出生后第3天,未检测到对电穿孔细胞增殖和凋亡的重大影响。这些表明miR-9 / 9 *和miR-124影响神经胶质细胞的细胞命运,从而诱导它们分化为神经元。此外,我们发现这种细胞命运的调节发生在RPC中,表明miRNA的高水平表达,但不是低水平的。我们的结果强烈表明,高水平的miRNA过表达对于通过miR-9 / 9 *和miR-124干扰指导细胞命运至关重要。
更新日期:2020-11-09
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