title: Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo.
abstract: Embryonic stem cells (ESCs) are pluripotent stem cells derived from early stage embryos. It remains unclear whether inhibiting the Wnt/β‑catenin signaling pathway using dickkopf Wnt signaling pathway inhibitor 1 (DKK1) impacts on the differentiation potential of mouse ESCs in vitro and in vivo. In the present study, immunohistochemical staining was used to measure the expression of markers of the three germ layers in ESCs and teratomas derived from ESCs. The expression of markers for the Wnt/β‑catenin signaling pathway were detected by reverse transcription‑polymerase chain reaction (RT‑qPCR). Immunohistochemistry and western blotting indicated that the expression levels of octamer‑binding transcription factor 4 in the DKK1‑treated ESC group were significantly greater compared with the control ESCs. Reduced expression levels of NeuroD and bone morphogenetic protein 4 were observed in the DKK1‑treated ESCs and teratomas derived from DKK1‑treated ESCs compared with the control group. Increased expression levels of SOX17 were observed in the DKK1‑treated ESCs compared with the control group. RT‑qPCR indicated that β‑catenin expression was significantly reduced in DKK1‑treated ESCs and teratomas derived from DKK1‑treated ESCs compared with the control groups. Western blotting indicated no alterations in the expression of GSK‑3β, however, the levels of phosphorylated‑GSK‑3β were significantly greater in the DKK1 treatment groups, while cyclin D1 and c‑Myc expression levels were significantly reduced in the DKK1 treatment groups compared with the control groups. These results suggest that inhibiting Wnt signaling in ESCs using DKK1 may promote mouse ESCs to differentiate into endoderm in vitro and in vivo, and suppress the tumorigenicity of ESCs.
authors.affiliation: Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Ou
authors.affiliation: Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liaoqiong
authors.initials: L
authors.lastname: Fang
authors.affiliation: Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hejing
authors.initials: H
authors.lastname: Tang
authors.affiliation: Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhibiao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013724:Teratoma / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D051176:beta Catenin; D019938:Cyclin D1; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3