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) 的一种有前途的疗法。然而，hiPSCs的分化差限制了它们的临床应用。因此，寻找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。甾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剂。然而，SREPBP1 是否调节 hiPSC 分化仍然未知。

在这项研究中，我们发现 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 增加了 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。