title: Two clonal types of human skin fibroblasts with different potentials for proliferation and tissue remodeling ability.
abstract: BACKGROUND
  Skin fibroblast heterogeneity is of growing interest due to its relevance in not only skin development but also cutaneous wound healing. However, the characterization of human dermal fibroblasts at a clonal level has not been accomplished and their functional heterogeneity remains poorly understood.
  
  
  OBJECTIVE
  The aim of this study was to define the clonal heterogeneity of human dermal fibroblasts.
  
  
  METHODS
  Isolated human dermal fibroblasts were clonally expanded and categorized by comprehensive phenotypic and gene expression profiling.
  
  
  RESULTS
  Single fibroblasts were significantly multiplied and efficiently cloned without chromosomal abnormalities under hypoxic conditions. Individual clones were heterogeneous in their proliferative capacity, and gene expression profiling revealed differences in the expression of genes involved in extracellular matrix synthesis and degradation. Each cloned fibroblast also had different abilities in terms of collagen remodeling. All phenotypic and gene expression data were analyzed with Spearman's rank correlation, and fibroblasts were categorized into at least two functional clonal types. One was highly proliferative, while the other was less proliferative but had the ability to remodel the tissue architecture. The proliferative clones were predominant in infants, but decreased with physiological aging.
  
  
  CONCLUSIONS
  This study provides strong evidence for the functional heterogeneity of human dermal fibroblasts at a clonal level, which has implications regarding skin repair and aging.
authors: Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon, Ehime 791-0295, Japan; Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan; Department of Bone and Joint Surgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Chihiro
authors: C
authors: Hiraoka
authors: Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Fujio
authors: F
authors: Toki
authors: Department of Dermatology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Ken
authors: K
authors: Shiraishi
authors: Department of Dermatology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Koji
authors: K
authors: Sayama
authors: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Emi K
authors: EK
authors: Nishimura
authors: Department of Bone and Joint Surgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Hiromasa
authors: H
authors: Miura
authors: Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon, Ehime 791-0295, Japan; Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Shigeki
authors: S
authors: Higashiyama
authors: Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Toon, Ehime 791-0295, Japan; Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: nanbscm@tmd.ac.jp.
authors: Daisuke
authors: D
authors: Nanba
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000502:physiology*; D003094:Collagen / Q000378:metabolism / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000166:cytology*; D015595:Skin Aging / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
chemical_list: D003094:Collagen
keywords: Dermal fibroblasts; Fibrosis; Heterogeneity; Hypoxia; Single cell cloning