Single-cell characterization of neovascularization using hiPSC-derived endothelial cells in a 3D microenvironment

Summary

The formation of vascular structures is fundamental for in vitro tissue engineering. Vascularization can enable the nutrient supply within larger structures and increase transplantation efficiency. We differentiated human induced pluripotent stem cells toward endothelial cells in 3D suspension culture. To investigate in vitro neovascularization and various 3D microenvironmental approaches, we designed a comprehensive single-cell transcriptomic study. Time-resolved single-cell transcriptomics of the endothelial and co-evolving mural cells gave insights into cell type development, stability, and plasticity. Transfer to a 3D hydrogel microenvironment induced neovascularization and facilitated tracing of migrating, coalescing, and tubulogenic endothelial cell states. During maturation, we monitored two pericyte subtypes evolving mural cells. Profiling cell-cell interactions between pericytes and endothelial cells revealed angiogenic signals during tubulogenesis. In silico discovered ligands were tested for their capability to attract endothelial cells. Our data, analyses, and results provide an in vitro roadmap to guide vascularization in future tissue engineering. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Authors Rosowski S, Remmert C, Marder M, Akishiba M, Bushe J, Feuchtinger A, Platen A, Ussar S, Theis F, Wiedenmann S, Meier M
Journal Stem cell reports
Publication Date 2023 Oct 10;18(10):1972-1986
PubMed 37714147
PubMed Central PMC10656300
DOI 10.1016/j.stemcr.2023.08.008

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