title: Thrombospondin-4 Promotes Neuronal Differentiation of NG2 Cells via the ERK/MAPK Pathway.
abstract: NG2-expressing neural progenitors can produce neurons in the central nervous system, providing a potential cell resource of therapy for neurological disorders. However, the mechanism underlying neuronal differentiation of NG2 cells remains largely unknown. In this report, we found that a thrombospondin (TSP) family member, TSP4, is involved in the neuronal differentiation of NG2 cells. When TSP4 was overexpressed, NG2 cells underwent spontaneous neuronal differentiation, as demonstrated by the induction of various neuronal differentiation markers such as NeuN, Tuj1, and NF200, at the messenger RNA and protein levels. In contrast, TSP4 silencing had an opposite effect on the expression of neuronal differentiation markers in NG2 cells. Next, the signaling pathway responsible for TSP4-mediated NG2 cell differentiation was investigated. We found that ERK but not p38 and AKT signaling was affected by TSP4 overexpression. Furthermore, when ERK signaling was blocked by the inhibitor U0126, the neuronal marker expression of NG2 cells was substantially increased. Together, these findings suggested that TSP4 promoted neuronal differentiation of NG2 cells by inhibiting ERK/MAPK signaling, revealing a novel role of TSP4 in cell fate specification of NG2 cells.
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China. hjyang_wmd@hotmail.com.|Henan Key lab of Biological Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China. hjyang_wmd@hotmail.com.
authors.forename: Hai Jie
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Shuang Ping
authors.initials: SP
authors.lastname: Ma
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ju
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Zhi Chao
authors.initials: ZC
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Bin Bin
authors.initials: BB
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Jun Jiang
authors.initials: JJ
authors.lastname: Lian
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Bin Feng
authors.initials: BF
authors.lastname: Cheng
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China. xxyxy_wm@163.com.|Henan Key lab of Biological Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China. xxyxy_wm@163.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.|Henan Key lab of Biological Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China.
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Feng
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D020935:MAP Kinase Signaling System; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C546339:Rbfox3 protein, rat; D019699:Thrombospondins; D014404:Tubulin; C101864:thrombospondin 4; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cell therapy; NG2 cells; Neuronal differentiation; Signaling pathway; Thrombospondin-4