Deng Shanshan, Zhang Yanli, Xu Chundi, Ma Duan
Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Int J Mol Med. 2015 Aug;36(2):355-62. doi: 10.3892/ijmm.2015.2238. Epub 2015 Jun 8.
microRNAs (miRNAs or miRS) have been demonstrated to be essential for neural development. miR-125b-2, presented on human chromosome 21, is overexpressed in neurons of individuals with Down syndrome (DS) with cognitive impairments. It has been reported that miR-125b-2 promotes specific types of neuronal differentiation; however, the function of miR-125b-2 in the early development of the embryo has remained to be fully elucidated. In the present study, a mouse embryonic stem cell (mESC) line was stably transfected with a miR-125b-2 lentiviral expression vector and found that miR-125b-2 overexpression did not affect the self-renewal or proliferation of mESCs. However, miR-125b-2 overexpression inhibited the differentiation of mESCs into endoderm and ectoderm. Finally, miR-125b-2 overexpression was found to impair all-trans-retinoic acid-induced neuron development in embryoid bodies. The findings of the present study implied that miR-125b-2 overexpression suppressed the differentiation of mESCs into neurons, which highlights that miR‑125b-2 is important in the regulation of ESC differentiation. The present study provided a basis for the further identification of novel targets of miR-125b-2, which may contribute to an enhanced understanding of the molecular mechanisms of ESC differentiation.
微小RNA(miRNA或miRs)已被证明对神经发育至关重要。位于人类21号染色体上的miR-125b-2在患有认知障碍的唐氏综合征(DS)个体的神经元中过度表达。据报道,miR-125b-2促进特定类型的神经元分化;然而,miR-125b-2在胚胎早期发育中的功能仍有待充分阐明。在本研究中,用miR-125b-2慢病毒表达载体稳定转染小鼠胚胎干细胞(mESC)系,发现miR-125b-2过表达不影响mESC的自我更新或增殖。然而,miR-125b-2过表达抑制了mESC向内胚层和外胚层的分化。最后,发现miR-125b-2过表达会损害胚状体中全反式维甲酸诱导的神经元发育。本研究结果表明,miR-125b-2过表达抑制了mESC向神经元的分化,这突出了miR-125b-2在ESC分化调控中的重要性。本研究为进一步鉴定miR-125b-2的新靶点提供了基础,这可能有助于增强对ESC分化分子机制的理解。