Investigation of human vascular development and aging using human ES/iPS cells

我们成功地诱导了iPS细胞分化为血管内皮细胞（ECs）和壁细胞（MCs），并分离了这些细胞。我们还建立了一种饲养和无血清的方法，使我们能够更有效地诱导ECs。体外培养的人es源性ECs （ESECs）和ips源性ECs （iPSECs）比成人ECs （HAECs）具有更大的伤口再内皮化和管形成的潜力。接下来，我们利用基因芯片技术对这三种类型的内皮细胞进行基因表达分析。Sirt1是一种编码nad依赖性组蛋白去乙酰化酶的衰老相关基因，在esec / ipsec中的表达水平高于haec。当Sirt1活性被siRNA敲低或被特定的Sirt1拮抗剂抑制时，上述细胞功能差异被消除，这表明Sirt1活性的差异导致了观察到的细胞功能差异。

We succeeded in inducing iPS cells to differentiate into vascular endothelial cells (ECs) and mural cells (MCs), which we were able to isolate. We also established a feeder- and serum-free method that enables us to more efficiently induce ECs. Human ES-derived ECs (ESECs) and iPS-derived ECs (iPSECs) had a greater potential for wound re-endothelialization and tube formation than human adult ECs (HAECs) in vitro. Next we carried out a gene expression analysis of these three types of ECs using gene chip technology. The expression level of Sirt1, an aging-related gene that encodes a NAD-dependent histone deacetylase, was higher in ESECs/iPSECs than in HAECs. When Sirt1 activity was knocked down by siRNA or inhibited by a specific Sirt1 antagonist, the aforementioned differences in the cellular functionality were abolished, which suggests that differences in Sirt1 activity contribute to the observed differences in the cellular functionality.