A small molecule-based strategy for endothelial differentiation and three-dimensional morphogenesis from human embryonic stem cells

Autor: Yijie Geng, Bradley Feng
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Heliyon, Vol 2, Iss 7 (2016)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2016.e00133
Popis: The emerging models of human embryonic stem cell (hESC) self-organizing organoids provide a valuable in vitro platform for studying self-organizing processes that presumably mimic in vivo human developmental events. Here we report that through a chemical screen, we identified two novel and structurally similar small molecules BIR1 and BIR2 which robustly induced the self-organization of a balloon-shaped three-dimensional structure when applied to two-dimensional adherent hESC cultures in the absence of growth factors. Gene expression analyses and functional assays demonstrated an endothelial identity of this balloon-like structure, while cell surface marker analyses revealed a VE-cadherin+CD31+CD34+KDR+CD43− putative endothelial progenitor population. Furthermore, molecular marker labeling and morphological examinations characterized several other distinct DiI-Ac-LDL+ multi-cellular modules and a VEGFR3+ sprouting structure in the balloon cultures that likely represented intermediate structures of balloon-formation.
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