title: Dormancy activation mechanism of tracheal stem cells.
abstract: Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification.
authors.affiliation: Department of Physiology, College of Life Science and Biopharmaceutics of Shenyang Pharmaceutical University, Shenyang, China.|Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.|Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The 4th Affiliated Hospital, Eye Institute, China Medical University, The Key Laboratory of Lens Research, Shenyang, China.
authors.forename: Jing-Xian
authors.initials: JX
authors.lastname: Xu
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.|Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Jia
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Wen-Ya
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.|Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Han
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.|Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
authors.affiliation: IVF Michigan, Bloomfield Hills, MI, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013724:Teratoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014134:Tracheal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D012319:RNA Polymerase II; D005472:Fluorouracil
keywords: Sox2 expression; dormancy; methylation; stem cell