Title |
Generation of functional human serotonergic neurons from fibroblasts
|
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Published in |
Molecular Psychiatry, October 2015
|
DOI | 10.1038/mp.2015.161 |
Pubmed ID | |
Authors |
K C Vadodaria, J Mertens, A Paquola, C Bardy, X Li, R Jappelli, L Fung, M C Marchetto, M Hamm, M Gorris, P Koch, F H Gage |
Abstract |
The brain's serotonergic system centrally regulates several physiological processes and its dysfunction has been implicated in the pathophysiology of several neuropsychiatric disorders. While in the past our understanding of serotonergic neurotransmission has come mainly from mouse models, the development of pluripotent stem cell and induced fibroblast-to-neuron (iN) transdifferentiation technologies has revolutionized our ability to generate human neurons in vitro. Utilizing these techniques and a novel lentiviral reporter for serotonergic neurons, we identified and overexpressed key transcription factors to successfully generate human serotonergic neurons. We found that overexpressing the transcription factors NKX2.2, FEV, GATA2 and LMX1B in combination with ASCL1 and NGN2 directly and efficiently generated serotonergic neurons from human fibroblasts. Induced serotonergic neurons (iSNs) showed increased expression of specific serotonergic genes that are known to be expressed in raphe nuclei. iSNs displayed spontaneous action potentials, released serotonin in vitro and functionally responded to selective serotonin reuptake inhibitors (SSRIs). Here, we demonstrate the efficient generation of functional human serotonergic neurons from human fibroblasts as a novel tool for studying human serotonergic neurotransmission in health and disease.Molecular Psychiatry advance online publication, 27 October 2015; doi:10.1038/mp.2015.161. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 1 | 25% |
Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Science communicators (journalists, bloggers, editors) | 1 | 25% |
Members of the public | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 1% |
Japan | 1 | <1% |
United Kingdom | 1 | <1% |
Korea, Republic of | 1 | <1% |
Unknown | 193 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 47 | 24% |
Researcher | 34 | 17% |
Student > Bachelor | 19 | 10% |
Student > Master | 17 | 9% |
Student > Doctoral Student | 12 | 6% |
Other | 28 | 14% |
Unknown | 41 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 45 | 23% |
Neuroscience | 44 | 22% |
Biochemistry, Genetics and Molecular Biology | 33 | 17% |
Medicine and Dentistry | 12 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 2% |
Other | 15 | 8% |
Unknown | 45 | 23% |