Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.
Department of Surgery, Harvard Medical School, Boston, MA, USA.
Nat Commun. 2024 Sep 30;15(1):8392. 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.
壁细胞是血管完整性和功能的核心。在这项研究中，我们展示了转录因子 NKX3.1 的创新用途，指导人诱导多能干细胞分化为壁祖细胞（iMPC）。通过在中胚层中间体中瞬时激活 NKX3.1，我们开发了一种与传统基于生长因子的分化技术不同的方法。这种方法有效地产生了一个强大的 iMPC 群体，能够成熟为多种功能的壁细胞亚型，包括平滑肌细胞和成纤维细胞。这些 iMPC 表现出关键的壁细胞功能，如收缩性、细胞外基质的沉积以及在体内支持内皮细胞介导的血管网络形成的能力。我们的研究不仅强调了 NKX3.1 在壁细胞分化中的命运决定意义，还突出了这些 iMPC 的治疗潜力。我们设想这些见解可以为 iMPC 在血管生物学和再生医学中的更广泛应用铺平道路。
