Qian Xin, Guo Xiangjiang, Ni Qihong, Wang Han, Ye Meng, Zhang Lan
Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
Stem Cell Res. 2021 Mar;51:102174. doi: 10.1016/j.scr.2021.102174. Epub 2021 Jan 13.
Human induced pluripotent stem cell (hiPSC)-derived endothelial cell (hiPSC-EC) transplantation is a promising therapy for treating peripheral artery disease (PAD). However, the poor differentiation of hiPSCs limits their clinical application. Therefore, finding key factors that regulate cellular differentiation is crucial for improving the therapeutic efficacy of hiPSC-EC transplantation. Sterol regulatory element binding protein 1 (SREBP1) is a key regulator of lipid metabolism and stem cell differentiation. However, it remains unknown whether SREPBP1 modulates hiPSC differentiation. In this study, we showed that SREBP1 expression was negatively associated with hiPSC differentiation and EC function. The results show that SREBP1 binds to the promoter region of miR199b-5p and suppresses its transcription, resulting in the activation of Notch1 signaling. Blocking SREBP1 increased both hiPSC differentiation and EC angiogenesis. These findings demonstrate a novel role for SREBP1 in hiPSC differentiation and EC angiogenesis.
人诱导多能干细胞（hiPSC）衍生的内皮细胞（hiPSC-EC）移植是治疗外周动脉疾病（PAD）的一种有前景的疗法。然而，hiPSC的低分化限制了它们的临床应用。因此，找到调节细胞分化的关键因素对于提高hiPSC-EC移植的治疗效果至关重要。固醇调节元件结合蛋白1（SREBP1）是脂质代谢和干细胞分化的关键调节因子。然而，SREPBP1是否调节hiPSC分化仍不清楚。在本研究中，我们表明SREBP1表达与hiPSC分化和EC功能呈负相关。结果表明，SREBP1与miR199b-5p的启动子区域结合并抑制其转录，导致Notch1信号通路的激活。阻断SREBP1可增加hiPSC分化和EC血管生成。这些发现证明了SREBP1在hiPSC分化和EC血管生成中的新作用。
