title: Chemical inhibition of sulfation accelerates neural differentiation of mouse embryonic stem cells and human induced pluripotent stem cells.
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.
authors.affiliation: Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Hirano
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Shoko
authors.initials: S
authors.lastname: Nishihara
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002460:Cell Line; D002704:Chlorates / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013431:Sulfates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D002704:Chlorates; D013431:Sulfates; D051153:Wnt Proteins