褪黑激素促进猪皮肤来源干细胞分化为原始生殖细胞样细胞增殖的分子机制被揭示
作者:课题五李云雷 来源:原创 发布时间:2022-09-20
近日,我国科学家在《Journal of Pineal Research》发文揭示了褪黑激素促进猪皮肤来源干细胞(skin-derived stem cells,SDSCs)体外分化的原始生殖细胞样细胞(primordial germ cell-like cells,PGCLCs)增殖的分子机制。证实,SDSCs转分化PGCLCs过程中,MLT经褪黑素受体1(MT1)介导可显著提高血小板衍生生长因子(PDGF)的转录和翻译水平,PDGF通过自分泌和旁分泌作用途径激活PDGF受体,随后刺激Ras并进一步激活转录因子血清反应因子(SRF),靶向调控细胞周期相关基因的表达,从而促进PGCLCs增殖。该研究系统地阐明了MLT通过MT1介导的MAPK信号通路在PGCLCs体外增殖中的作用途径和分子机制。
MLT promotes the proliferation of PGCLCs independently of its antioxidant effect. (A) Brightfiled of cultures with different concentrations (0, 5, 25, 100 μM) of MLT for 16 days. Scale bar, 100 μm. (B) Representative images of costaining of PGCLCs for SOX17 (green) and Ki67 (red) with different MLT concentrations. DAPI (blue) stained the nuclei. Scale bar, 25 μm. (C) Flow cytometry analysis of SOX17 (FITC) and Ki67 (CY3) double staining with different MLT concentrations. (D) Statistical analysis of SOX17 positive cells with different MLT concentrations. (E) Statistical analysis of SOX17 and Ki67 double-positive cells with different MLT concentrations. (F) The protein levels of the SOX17 and BLIMP1 detected by WB in different MLT concentrations. (G) Flow cytometry analysis of SOX17 positive cells with control group, 1 mM NAC-treated cells and 0.2 U/ul SOD-treated cells group. (H) Statistical analysis of SOX17 positive cells with control group, 1 mM NAC group and 0.2 U/ul SOD group. The results are presented as mean ± SD. All the experiments were repeated at least three times. nsp > .05; *p < .05; **p < .01. MLT, melatonin; NAC, N-acetyl--cysteine; PGCLCs, primordial germ cell-like cells; SOD, superoxide dismutase; WB, Western blot.