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Generation of Isthmic Organizer-Like Cells from Human Embryonic Stem Cells

 Junwon Lee  ;  Sang-Hwi Choi  ;  Dongjin R Lee  ;  Dae-Sung Kim  ;  Dong-Wook Kim 
 Molecules and Cells, Vol.41(2) : 110-118, 2018 
Journal Title
 Molecules and Cells 
Issue Date
FGF ; Wnt ; human pluripotent stem cells ; isthmic organizer ; neural differentiation
The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 (0.6 muM) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course in vivo. Resultant cells showed upregulated expression levels of FGF8 and WNT1. The addition of exogenous FGF8 further increased WNT1 expression by 2.6 fold. Gene ontology following microarray analysis confirmed that IsO-like cells enriched the expression of MHB-related genes by 40 fold compared to control cells. Lysates and conditioned media of IsO-like cells contained functional FGF8 and WNT1 proteins that could induce MHB-related genes in differentiating ESCs. The method for generating functional IsO-like cells described in this study could be used to study human central nervous system development and congenital malformations of the midbrain and hindbrain.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Wook(김동욱) ORCID logo https://orcid.org/0000-0002-5025-1532
Lee, Jun Won(이준원) ORCID logo https://orcid.org/0000-0003-0543-7132
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