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Sci Rep. 2015 Nov 6;5:16237. doi: 10.1038/srep16237.

A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells.

Rhim JH1, Luo X1, Xu X1, Gao D1, Zhou T1, Li F1,2, Qin L3,2, Wang P4,2, Xia X1,2, Wong ST1,2.

Author information

1
Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
2
Weill Cornell Medical College, Cornell University, New York, NY 10065.
3
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
4
Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030.

Abstract

Small molecule compounds promoting the neuronal differentiation of stem/progenitor cells are of pivotal importance to regenerative medicine. We carried out a high-content screen to systematically characterize known bioactive compounds, on their effects on the neuronal differentiation and the midbrain dopamine (mDA) neuron specification of neural progenitor cells (NPCs) derived from the ventral mesencephalon of human fetal brain. Among the promoting compounds three major pharmacological classes were identified including the statins, TGF-βRI inhibitors, and GSK-3 inhibitors. The function of each class was also shown to be distinct, either to promote both the neuronal differentiation and mDA neuron specification, or selectively the latter, or promote the former but suppress the latter. We then carried out initial investigation on the possible mechanisms underlying, and demonstrated their applications on NPCs derived from human pluripotent stem cells (PSCs). Our study revealed the potential of several small molecule compounds for use in the directed differentiation of human NPCs. The screening result also provided insight into the signaling network regulating the differentiation of human NPCs.

PMID:
26542303
PMCID:
PMC4635364
DOI:
10.1038/srep16237
[Indexed for MEDLINE]
Free PMC Article

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