Direct conversion of human fibroblasts to induced serotonergic neurons.

Abstract:

:Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly converted to induced serotonergic (i5HT) neurons by the expression of Ascl1, Foxa2, Lmx1b and FEV. The transdifferentiation was enhanced by p53 knockdown and appropriate culture conditions including hypoxia. The i5HT neurons expressed markers for mature serotonergic neurons, had Ca(2+)-dependent 5HT release and selective 5HT uptake, exhibited spontaneous action potentials and spontaneous excitatory postsynaptic currents. Application of serotonin significantly increased the firing rate of spontaneous action potentials, demonstrating the functional utility of i5HT neurons for studying serotonergic neurotransmission. The availability of human i5HT neurons will be very useful for research and drug discovery on many serotonin-related mental disorders.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Xu Z,Jiang H,Zhong P,Yan Z,Chen S,Feng J

doi

10.1038/mp.2015.101

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

62-70

issue

1

eissn

1359-4184

issn

1476-5578

pii

mp2015101

journal_volume

21

pub_type

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