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- Title
A simplified method to generate serotonergic neurons from mouse embryonic stem and induced pluripotent stem cells.
- Authors
Shimada, Takeshi; Takai, Yoshihiro; Shinohara, Kikuko; Yamasaki, Atsushi; Tominaga-Yoshino, Keiko; Ogura, Akihiko; Toi, Akihiro; Asano, Kouji; Shintani, Norihito; Hayata-Takano, Atsuko; Baba, Akemichi; Hashimoto, Hitoshi
- Abstract
J. Neurochem. (2012) 122, 81-93. Abstract We have developed a new simple method to induce serotonergic neurons from embryonic stem (ES) and induced pluripotent stem cells. When ES or induced pluripotent stem cells were cultured on a thick gel layer of Matrigel, most colonies extended TuJ1-positive neurites. We found that noggin, a known antagonist of bone morphogenic protein, induces ES cells to express genes involved in serotonergic differentiation, such as Nkx2.2, Pet-1, Sonic hedgehog, tryptophan hydroxylase 2, and serotonin transporter, as well as increases high potassium-induced release of serotonin. To concentrate serotonergic neurons, ES cells carrying Pet-1-enhancer-driven enhanced green fluorescent protein were differentiated and sorted into about 80% pure cultures of serotonergic neurons. Whole cell voltage-clamp recordings showed a voltage-dependent current in dissociated neurons. This simplified method provides an alternative option for serotonergic differentiation of pluripotent stem cells and will likely contribute a deeper understanding regarding the nature of serotonergic neurons and open new therapeutic perspectives for the treatment of psychiatric disorders.
- Subjects
EMBRYONIC stem cells; NEURONS; LABORATORY mice; PLURIPOTENT stem cells; MENTAL illness; BONE morphogenetic proteins; GENE expression; TRYPTOPHAN hydroxylase
- Publication
Journal of Neurochemistry, 2012, Vol 122, Issue 1, p81
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2012.07724.x