Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells
| Autor: | Norikazu Saiki, Akira Niwa, Emiko Yagi, Yukimasa Taniguchi, Ryo Ohta, Yoko Nishinaka-Arai, Megumu K. Saito, Tatsutoshi Nakahata, Junko Toga, Akira Watanabe, Chihiro Okada, Kiyotoshi Sekiguchi, Naoya M. Suzuki |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular differentiation Induced Pluripotent Stem Cells Cell Culture Techniques Embryoid body Biology Article Basement Membrane Cell Line Extracellular matrix 03 medical and health sciences Directed differentiation Humans Progenitor cell Induced pluripotent stem cell Multidisciplinary Base Sequence Integrin alpha6beta1 Sequence Analysis RNA Endothelial Cells Feeder Cells Cell Differentiation Cell sorting humanities Peptide Fragments Extracellular Matrix Cell biology Endothelial stem cell 030104 developmental biology Laminin |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Ohta, R. et al. Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells. Sci. Rep. 6, 35680; doi: 10.1038/srep35680 (2016) 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. |
| Databáze: | OpenAIRE |
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