All Publications


  • A human arteriovenous differentiation roadmap reveals vein developmental mechanisms and vascular effects of viruses. bioRxiv : the preprint server for biology Ang, L. T., Zheng, S. L., Liu, K. J., Masaltseva, A., Winters, J., von Creytz, I., Jha, S. K., Yin, Q., Qian, C., Xiong, X., Dailamy, A., Xi, E., Alcocer, J. C., Sorensen, D. W., She, R., Smolyar, K., Szumska, D., Nornes, S., Martin, R. M., Lesch, B. J., Restrepo, N. K., Sun, W., Weissman, J. S., Lickert, H., Porteus, M. P., Skylar-Scott, M. A., Mosimann, C., Sumanas, S., De Val, S., Prescott, J. B., Red-Horse, K., Loh, K. M. 2025

    Abstract

    We map human artery and vein endothelial cell (EC) differentiation from pluripotent stem cells, and employ this roadmap to discover new mechanisms of vascular development (vein differentiation) and disease (viral infection). We discovered vein development unfolds in two steps driven by opposing signals: VEGF differentiates mesoderm into "pre-vein" ECs, but surprisingly, VEGF/ERK inhibition subsequently specifies vein ECs. Pre-vein ECs co-expressed certain arterial (SOX17) and venous (APLNR) markers, harbored poised chromatin at future venous genes, but completed venous differentiation only upon VEGF inhibition. Intersectional lineage tracing revealed that early Sox17+ Aplnr+ ECs also formed veins in vivo. Next, we compared how Ebola, Andes, and Nipah viruses infect artery and vein ECs under biosafety-level-4 containment. Each virus distinctly affected ECs. Interestingly, artery and vein ECs also responded divergently to the same virus, thus revealing that developmentally-specified cell identity impacts viral infection. Collectively, this arteriovenous differentiation roadmap illuminates vascular development and disease.

    View details for DOI 10.1101/2025.10.11.681838

    View details for PubMedID 41279810

    View details for PubMedCentralID PMC12632389

  • Rapid model-guided design of organ-scale synthetic vasculature for biomanufacturing. Science (New York, N.Y.) Sexton, Z. A., Rütsche, D., Herrmann, J. E., Hudson, A. R., Sinha, S., Du, J., Shiwarski, D. J., Masaltseva, A., Solberg, F. S., Pham, J., Szafron, J. M., Wu, S. M., Feinberg, A. W., Skylar-Scott, M. A., Marsden, A. L. 2025; 388 (6752): 1198-1204

    Abstract

    Our ability to produce human-scale biomanufactured organs is limited by inadequate vascularization and perfusion. For arbitrarily complex geometries, designing and printing vasculature capable of adequate perfusion poses a major hurdle. We introduce a model-driven design platform that demonstrates rapid synthetic vascular model generation alongside multifidelity computational fluid dynamics simulations and three-dimensional bioprinting. Key algorithmic advances accelerate vascular generation 230-fold and enable application to arbitrarily complex shapes. We demonstrate that organ-scale vascular network models can be generated and used to computationally vascularize >200 engineered and anatomic models. Synthetic vascular perfusion improves cell viability in fabricated living-tissue constructs. This platform enables the rapid, scalable vascular model generation and fluid physics analysis for biomanufactured tissues that are necessary for future scale-up and production.

    View details for DOI 10.1126/science.adj6152

    View details for PubMedID 40504910

  • Rapid Model-Guided Design of Organ-Scale Synthetic Vasculature for Biomanufacturing. Science Sexton, Z. A., Rütsche, D., Herrmann, J. E., Hudson, A. R., Sinha, S., Du, J., Shiwarski, D. J., Masaltseva, A., Solberg, F. S., Pham, J., Szafron, J. M., Wu, S. M., Feinberg, A. W., Skylar-Scott, M. A., Marsden, A. L. 2025; 388 (6752): 1198-1204

    View details for DOI 10.1126/science.adj6152