Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells

作者：Ryo Ohta, Akira Niwa, Yukimasa Taniguchi, Naoya Suzuki, Junko Toga, Emiko Yagi, Norikazu Saiki, Yoko Nishinaka‐Arai, Chihiro Okada, Akira Watanabe, Tatsutoshi Nakahata, Kiyotoshi Sekiguchi, Megumu K. Saito · 发表于：Scientific Reports · 年份：2016 · DOI：10.1038/srep35680 · 被引用次数：52 · 研究领域：Cell Adhesion Molecules Research、Single-cell and spatial transcriptomics、Renal and related cancers

Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for their clinical application. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrate that the directed switching of defined ECMs robustly yields highly-purified (>95%) endothelial progenitor cells (PSC-EPCs) without cell sorting from hPSCs in an integrin-laminin axis-dependent manner. Single-cell RNA-seq analysis revealed that LM411-E8 resolved intercellular transcriptional heterogeneity and escorted the progenitor cells to the appropriate differentiation pathway. The PSC-EPCs gave rise to functional endothelial cells both in vivo and in vitro. We therefore propose that sequential switching of defined matrices is an important concept for guiding cells towards desired fate.