Robust differentiation of human pluripotent stem cells into mural progenitor cells via transient activation of NKX3.1

• Published in: Nature communications Vol. 15; no. 1; pp. 8392 - 19
• Main Authors: Lee, Umji, Zhang, Yadong, Zhu, Yonglin, Luo, Allen Chilun, Gong, Liyan, Tremmel, Daniel M., Kim, Yunhye, Villarreal, Victoria Sofia, Wang, Xi, Lin, Ruei-Zeng, Cui, Miao, Ma, Minglin, Yuan, Ke, Wang, Kai, Chen, Kaifu, Melero-Martin, Juan M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/106; 13/109; 13/31; 13/51; 13/62; 14/63; 38/91; 631/136/142; 631/136/16; 631/532/2064/2158; Animals; Blood vessels; Cell activation; Cell Differentiation; Differentiation (biology); Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Extracellular matrix; Extracellular Matrix - metabolism; Growth factors; Hemopoiesis; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humanities and Social Sciences; Humans; In vivo methods and tests; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Intermediates; Mice; multidisciplinary; Muscle contraction; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Network formation; Nkx3.1 protein; Pericytes; Pericytes - cytology; Pericytes - metabolism; Pluripotency; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Progenitor cells; Regenerative medicine; Robustness; Science; Science (multidisciplinary); Smooth muscle; Stem cells; Transcription activation; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52678-8

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.