title: Retinoic acid promotes the proliferation of primordial germ cell-like cells differentiated from mouse skin-derived stem cells in vitro.
abstract: Skin-derived stem cells (SDSCs) have the potential to differentiate into gametes and are a potential resource for research and clinical applications. Sufficient amount of primordial germ cells (PGCs) is an important requirement for successful differentiation of SDSCs into gametes in vitro. Retinoic acid (RA), a vitamin A-derived small lipophilic molecule, promotes the growth of PGCs in vivo; however, the role of RA on the proliferation of PGC-like cells (PGCLCs) derived from SDSCs remains unknown. In this study, SDSCs were induced to differentiate into the embryoid body and cocultured with mouse fibroblasts to form PGCLCs. The proliferation of PGCLCs with the presence of various concentrations of RA was investigated in vitro. Immunofluorescence labeling showed that the 5-Bromo-2-deoxyUridine-positive ratio of PGCLCs was increased after the cells were treated with 5-μM RA, and flow cytometry results showed that the number of cells in the S phase was increased significantly. The messenger RNA expression levels of cell cycle-related genes, CCND1 and CDK2, were also increased. Furthermore, RA effectively promoted the external proliferation of endogenous PGCs when 11.5-days postcoitum fetal mouse genital ridges were cultured in vitro. In conclusion, 5-μM RA promoted the proliferation of SDSCs-derived PGCLCs and endogenous PGCs. Our study will provide a valuable model system for studying the differentiation of stem cells into gametes in vitro.
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; College of Life Sciences, Qingdao Agricultural University, Qingdao, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tan
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China.
authors.forename: Shun-Feng
authors.initials: SF
authors.lastname: Cheng
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China.
authors.forename: Yuan-Chao
authors.initials: YC
authors.lastname: Sun
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; College of Life Sciences, Qingdao Agricultural University, Qingdao, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Molecular and Cell Genetics Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, Shandong, China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong, China. Electronic address: wshen@qau.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D019938:Cyclin D1 / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005854:Germ Cells / Q000166:cytology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C530105:Ccnd1 protein, mouse; D012333:RNA, Messenger; D019938:Cyclin D1; D014212:Tretinoin; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2
keywords: Primordial germ cell–like cell; Proliferation; Retinoic acid; Skin-derived stem cell