Neuronal differentiation of human iPS cells induced by baicalin via regulation of bHLH gene expression.
Efficient differentiation is important for regenerative medicine based on pluripotent stem cells, including treatment of neurodegenerative disorders and trauma. Baicalin promotes neuronal differentiation of neural stem/progenitor cells of rats and mice. To evaluate the suitability of baicalin for neuronal differentiation of human iPS cells, we investigated whether it promotes neuronal differentiation in human iPS cells and monitored basic helix-loop-helix (bHLH) gene expression during neuronal differentiation. Baicalin promoted neuronal differentiation and inhibited glial differentiation, suggesting that baicalin can influence the neuronal fate decision in human iPS cells. Notch signaling, which is upstream of bHLH proteins, was not involved in baicalin-induced neuronal differentiation. Baicalin treatment did not down-regulate Hes1 gene expression, but it reduced Hes1 protein levels and up-regulated Ascl1 gene expression. Thus, baicalin promoted neuronal differentiation via modulation of bHLH transcriptional factors. Therefore, baicalin has potential to be used as a small-molecule drug for regenerative treatment of neurodegenerative disorders.
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Japan. Electronic address: morita-a@suzuka-u.ac.jp.
Akihiro
A
Morita
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Japan.
Kohei
K
Soga
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Japan.
Hironobu
H
Nakayama
Institute of Traditional Chinese Medicine, Suzuka University of Medical Science, Japan.
Torao
T
Ishida
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Japan.
Shosuke
S
Kawanishi
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Japan.
Eisuke F
EF
Sato
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D005419:Flavonoids; C038044:baicalin
Ascl1; Baicalin; Hes1; Human iPS cells; Neurogenesis; Notch