Chemical inhibition of sulfation accelerates neural differentiation of mouse embryonic stem cells and human induced pluripotent stem cells

Norihiko Sasaki, Takuya Hirano, Kumiko Kobayashi, Masashi Toyoda, Yoshitaka Miyakawa, Hajime Okita, Nobutaka Kiyokawa, Hidenori Akutsu, Akihiro Umezawa, Shoko Nishihara

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Pluripotency of embryonic stem cells (ESCs) is maintained by the balancing of several signaling pathways, such as Wnt, BMP, and FGF, and differentiation of ESCs into a specific lineage is induced by the disruption of this balance. Sulfated glycans are considered to play important roles in lineage choice of ESC differentiation by regulating several signalings. We examined whether reduction of sulfation by treatment with the chemical inhibitor chlorate can affect differentiation of ESCs. Chlorate treatment inhibited mesodermal differentiation of mouse ESCs, and then induced ectodermal differentiation and accelerated further neural differentiation. This could be explained by the finding that several signaling pathways involved in the induction of mesodermal differentiation (Wnt, BMP, and FGF) or inhibition of neural differentiation (Wnt and BMP) were inhibited in chlorate-treated embryoid bodies, presumably due to reduced sulfation on heparan sulfate and chondroitin sulfate. Furthermore, neural differentiation of human induced pluripotent stem cells (hiPSCs) was also accelerated by chlorate treatment. We propose that chlorate could be used to induce efficient neural differentiation of hiPSCs instead of specific signaling inhibitors, such as Noggin.

Original languageEnglish
Pages (from-to)480-486
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume401
Issue number3
DOIs
Publication statusPublished - 2010 Oct 22
Externally publishedYes

Keywords

  • Chlorate
  • Human induced pluripotent stem cell
  • Mouse embryonic stem cell
  • Neural differentiation
  • Sulfation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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