title: CD38 Is Required for Neural Differentiation of Mouse Embryonic Stem Cells by Modulating Reactive Oxygen Species.
abstract: CD38 is a multifunctional membrane enzyme and the main mammalian ADP-ribosyl cyclase, which catalyzes the synthesis and hydrolysis of cADPR, a potent endogenous Ca(2+) mobilizing messenger. Here, we explored the role of CD38 in the neural differentiation of mouse embryonic stem cells (ESCs). We found that the expression of CD38 was decreased during the differentiation of mouse ESCs initiated by adherent monoculture. Perturbing the CD38/cADPR signaling by either CD38 knockdown or treatment of cADPR antagonists inhibited the neural commitment of mouse ESCs, whereas overexpression of CD38 promoted it. Moreover, CD38 knockdown dampened reactive oxygen species (ROS) production during neural differentiation of ESCs by inhibiting NADPH oxidase activity, while CD38 overexpression enhanced it. Similarly, application of hydrogen peroxide mitigated the inhibitory effects of CD38 knockdown on neural differentiation of ESCs. Taken together, our data indicate that the CD38 signaling pathway is required for neural differentiation of mouse ESCs by modulating ROS production.
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Baixia
authors.initials: B
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Kehui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Miller
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Liang-Ren
authors.initials: LR
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Li-He
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yue
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1
keywords: Calcium flux; Cell signaling; Embryonic stem cells; Neural differentiation; Signal transduction