Liu Clifford Z, Prasad Aditi, Jadhav Bharati, Liu Yu, Gu Mingxia, Sharp Andrew J, Gelb Bruce D
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
iScience. 2023 Nov 30;27(1):108599. doi: 10.1016/j.isci.2023.108599. eCollection 2024 Jan 19.
Valvular heart disease presents a significant health burden, yet advancements in valve biology and therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells, which are transcriptionally and phenotypically distinct from vascular endothelial cells. These endocardial cells can be challenged to undergo endothelial-to-mesenchymal transition (EndMT), after which two distinct populations emerge-one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs). We then characterized these populations through bulk RNA-seq transcriptome analyses and compared our VIC and VEC populations to pseudobulk data generated from normal valve tissue of a 15-week-old human fetus. By increasing the accessibility to these cell populations, we aim to accelerate discoveries for cardiac valve biology and disease.
心脏瓣膜疾病带来了巨大的健康负担,然而,由于难以获取人类瓣膜细胞,瓣膜生物学和治疗学的进展受到了阻碍。在本研究中,我们开发了一种可扩展且无需饲养层的方法,将人类诱导多能干细胞(iPSC)分化为心内膜细胞,这些心内膜细胞在转录和表型上与血管内皮细胞不同。这些心内膜细胞可被诱导经历内皮-间充质转化(EndMT),之后会出现两个不同的群体——一个群体经历EndMT成为瓣膜间质细胞(VIC),而另一个群体强化其内皮特性成为瓣膜内皮细胞(VEC)。然后,我们通过大量RNA测序转录组分析对这些群体进行了表征,并将我们的VIC和VEC群体与从一名15周大人类胎儿的正常瓣膜组织生成的伪批量数据进行了比较。通过提高获取这些细胞群体的便利性,我们旨在加速心脏瓣膜生物学和疾病方面的发现。