title: A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells.
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.
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Rhim
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Luo
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
authors.forename: Dongbing
authors.initials: D
authors.lastname: Gao
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.
authors.forename: Tieling
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.|Weill Cornell Medical College, Cornell University, New York, NY 10065.
authors.forename: Fuhai
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.|Weill Cornell Medical College, Cornell University, New York, NY 10065.
authors.forename: Lidong
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030.|Weill Cornell Medical College, Cornell University, New York, NY 10065.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.|Weill Cornell Medical College, Cornell University, New York, NY 10065.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xia
authors.affiliation: Chao Center for BRAIN, Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030.|Weill Cornell Medical College, Cornell University, New York, NY 10065.
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004298:Dopamine