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A simplified method to generate serotonergic neurons from mouse embryonic stem and induced pluripotent stem cells
Author(s) -
Shimada Takeshi,
Takai Yoshihiro,
Shinohara Kikuko,
Yamasaki Atsushi,
TominagaYoshino Keiko,
Ogura Akihiko,
Toi Akihiro,
Asano Kouji,
Shintani Norihito,
HayataTakano Atsuko,
Baba Akemichi,
Hashimoto Hitoshi
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07724.x
Subject(s) - serotonergic , induced pluripotent stem cell , embryonic stem cell , microbiology and biotechnology , stem cell , biology , noggin , tryptophan hydroxylase , neuroscience , serotonin , bone morphogenetic protein , biochemistry , gene , receptor
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.