title: Cell motion predicts human epidermal stemness.
abstract: Image-based identification of cultured stem cells and noninvasive evaluation of their proliferative capacity advance cell therapy and stem cell research. Here we demonstrate that human keratinocyte stem cells can be identified in situ by analyzing cell motion during their cultivation. Modeling experiments suggested that the clonal type of cultured human clonogenic keratinocytes can be efficiently determined by analysis of early cell movement. Image analysis experiments demonstrated that keratinocyte stem cells indeed display a unique rotational movement that can be identified as early as the two-cell stage colony. We also demonstrate that α6 integrin is required for both rotational and collective cell motion. Our experiments provide, for the first time, strong evidence that cell motion and epidermal stemness are linked. We conclude that early identification of human keratinocyte stem cells by image analysis of cell movement is a valid parameter for quality control of cultured keratinocytes for transplantation.
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan nanba.daisuke.mk@ehime-u.ac.jp yann.barrandon@epfl.ch.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nanba
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Toki
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Sota
authors.initials: S
authors.lastname: Tate
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Matome
authors.initials: M
authors.lastname: Imai
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Matsushita
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sayama
authors.affiliation: Research Center for Nuclear Physics, Osaka University, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Toki
authors.affiliation: Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan Division of Cell Growth and Tumor Regulation, Proteo-Science Center; Department of Biochemistry and Molecular Genetics and Department of Dermatology, Graduate School of Medicine; and Translational Research Center, Ehime University Hospital, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.affiliation: Laboratory of Stem Cell Dynamics, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland Department of Experimental Surgery, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland nanba.daisuke.mk@ehime-u.ac.jp yann.barrandon@epfl.ch.
authors.forename: Yann
authors.initials: Y
authors.lastname: Barrandon
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D003198:Computer Simulation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D039503:Integrin alpha6; D012333:RNA, Messenger