title: Up-regulation of lymphocyte antigen 6 complex expression in side-population cells derived from a human trophoblast cell line HTR-8/SVneo.
abstract: The continual proliferation and differentiation of trophoblasts are critical for the maintenance of pregnancy. It is well known that the tissue stem cells are associated with the development of tissues and pathologies. It has been demonstrated that side-population (SP) cells identified by fluorescence-activated cell sorting (FACS) are enriched with stem cells. The SP cells in HTR-8/SVneo cells derived from human primary trophoblast cells were isolated by FACS. HTR-8/SVneo-SP cell cultures generated both SP and non-SP (NSP) subpopulations. In contrast, NSP cell cultures produced NSP cells and failed to produce SP cells. These SP cells showed self-renewal capability by serial colony-forming assay. Microarray expression analysis using a set of HTR-8/SVneo-SP and -NSP cells revealed that SP cells overexpressed several stemness genes including caudal type homeobox2 (CDX2) and bone morphogenic proteins (BMPs), and lymphocyte antigen 6 complex locus D (LY6D) gene was the most highly up-regulated in HTR-8/SVneo-SP cells. LY6D gene reduced its expression in the course of a 7-day cultivation in differentiation medium. SP cells tended to reduce its fraction by treatment of LY6D siRNA indicating that LY6D had potential to maintain cell proliferation of HTR-8/SVneo-SP cells. On ontology analysis, epithelial-mesenchymal transition (EMT) pathway was involved in the up-regulated genes on microarray analysis. HTR-SVneo-SP cells showed enhanced migration. This is the first report that LY6D was important for the maintenance of HTR-8/SVneo-SP cells. EMT was associated with the phenotype of these SP cells.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Soshi
authors.initials: S
authors.lastname: Kusunoki
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo, 113-8510, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tabu
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Okabe
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamada
authors.affiliation: Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo, 113-8510, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taga
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Makino
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo, 113-8431, Japan. kkato@med.kyushu-u.ac.jp.|Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan. kkato@med.kyushu-u.ac.jp.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kato
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000209:etiology; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000235:genetics / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C094237:LY6D protein, human
keywords: Epithelial–mesenchymal transition; HTR-8/SVneo; LY6D; Side population cell; Trophoblast