Robust differentiation of human pluripotent stem cells into mural progenitor cells via transient activation of NKX3.1
Umji Lee, Yadong Zhang, Yonglin Zhu, Allen Chilun Luo, Liyan Gong, Daniel M. Tremmel, Yunhye Kim, Victoria Sofia Villarreal, Xi Wang, Ruei‐Zeng Lin, Miao Cui, Minglin Ma, Ke Yuan, Kai Wang, Kaifu Chen, Juan M. Melero‐Martin
Abstract
Mural cells are central to vascular integrity and function. In this study, we demonstrate the innovative use of the transcription factor NKX3.1 to guide the differentiation of human induced pluripotent stem cells into mural progenitor cells (iMPCs). By transiently activating NKX3.1 in mesodermal intermediates, we developed a method that diverges from traditional growth factor-based differentiation techniques. This approach efficiently generates a robust iMPC population capable of maturing into diverse functional mural cell subtypes, including smooth muscle cells and pericytes. These iMPCs exhibit key mural cell functionalities such as contractility, deposition of extracellular matrix, and the ability to support endothelial cell-mediated vascular network formation in vivo. Our study not only underscores the fate-determining significance of NKX3.1 in mural cell differentiation but also highlights the therapeutic potential of these iMPCs. We envision these insights could pave the way for a broader use of iMPCs in vascular biology and regenerative medicine. Mural progenitor cells are crucial for vascular stability. Here, the authors generate these cells from human pluripotent stem cells using NKX3.1 and show that they can mature into various mural cell types and contribute to blood vessel formation.