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

Research output: Contribution to journalArticle

Abstract

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 μM) 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.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalMolecules and cells
Volume41
Issue number2
DOIs
Publication statusPublished - 2018 Jan 1

Keywords

  • FGF
  • Human pluripotent stem cells
  • Isthmic organizer
  • Neural differentiation
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Generation of isthmic organizer-like cells from human embryonic stem cells'. Together they form a unique fingerprint.

  • Cite this