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Comp Med. 2014 Apr;64(2):140-7.

Role of retinoic acid and fibroblast growth factor 2 in neural differentiation from cynomolgus monkey (Macaca fascicularis) embryonic stem cells.

Author information

1
Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
2
Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
3
Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan, Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan.
4
RIKEN BioResource Center, Tsukuba, Ibaraki, Japan, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
5
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
6
Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan. sankai@nibio.go.jp.

Abstract

Retinoic acid is a widely used factor in both mouse and human embryonic stem cells. It suppresses differentiation to mesoderm and enhances differentiation to ectoderm. Fibroblast growth factor 2 (FGF2) is widely used to induce differentiation to neurons in mice, yet in primates, including humans, it maintains embryonic stem cells in the undifferentiated state. In this study, we established an FGF2 low-dose-dependent embryonic stem cell line from cynomolgus monkeys and then analyzed neural differentiation in cultures supplemented with retinoic acid and FGF2. When only retinoic acid was added to culture, neurons differentiated from FGF2 low-dose-dependent embryonic stem cells. When both retinoic acid and FGF2 were added, neurons and astrocytes differentiated from the same embryonic stem cell line. Thus, retinoic acid promotes the differentiation from embryonic stem cells to neuroectoderm. Although FGF2 seems to promote self-renewal in stem cells, its effects on the differentiation of stem cells are influenced by the presence or absence of supplemental retinoic acid.

PMID:
24674590
PMCID:
PMC3997293
[Indexed for MEDLINE]
Free PMC Article

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