title: Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.
abstract: BACKGROUND
  Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.
  
  
  METHODS
  Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs) were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs) and the subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.
  
  
  RESULTS
  In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.
  
  
  CONCLUSIONS
  GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.
authors.affiliation: Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Pathology Division, Research Center for Innovative Oncology National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Pathology Division, Research Center for Innovative Oncology National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.affiliation: Genetic Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.affiliation: Genetic Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan; Pathology Division, Research Center for Innovative Oncology National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D002478:Cells, Cultured; D016000:Cluster Analysis; D005347:Fibroblasts / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000166:cytology*; D020869:Gene Expression Profiling / Q000379:methods*; D005801:Genes, Homeobox / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome