Farber Gregory, Takasugi Paige, Ricketts Shea, Wang Haofei, Xie Yifang, Farber Esther, Liu Jiandong, Qian Li
The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Mol Cell Cardiol. 2025 Feb;199:33-45. doi: 10.1016/j.yjmcc.2024.11.012. Epub 2024 Dec 16.
Sox17-Erg direct reprogramming is a potent tool for the in vitro and in vivo generation of arterial-like induced-endothelial cells from fibroblasts. In this study, we illustrate the pioneering roles of both Sox17 and Erg in the endothelial cell reprogramming process and demonstrate that emergent gene expression only occurs when both factors are co-expressed. Bioinformatic analyses and molecular validation reveal both Bach2 and Etv4 as integral mediators of Sox17-Erg reprogramming with different roles in lung and heart fibroblast reprogramming. The generated organ-specific induced endothelial cells express molecular signatures similar to vasculature found in the starting cell's organ of origin and the starting chromatin architecture plays a role in the acquisition of this organ-specific identity. Overall, the Sox17-Erg reprogramming mechanism provides foundational knowledge for the future recapitulation of vascular heterogeneity through direct reprogramming.
Sox17-Erg直接重编程是一种用于在体外和体内从成纤维细胞生成动脉样诱导内皮细胞的有效工具。在本研究中，我们阐述了Sox17和Erg在内皮细胞重编程过程中的先驱作用，并证明只有当这两种因子共同表达时才会出现新的基因表达。生物信息学分析和分子验证揭示了Bach2和Etv4作为Sox17-Erg重编程的重要介导因子，在肺和心脏成纤维细胞重编程中发挥不同作用。所生成的器官特异性诱导内皮细胞表达的分子特征类似于起始细胞起源器官中发现的脉管系统，并且起始染色质结构在获得这种器官特异性身份中发挥作用。总体而言，Sox17-Erg重编程机制为未来通过直接重编程再现血管异质性提供了基础知识。
