title: Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.
abstract: OBJECTIVE
  A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer.
  
  
  METHODS
  Qualitative study with adult human larynges.
  
  
  METHODS
  Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67).
  
  
  RESULTS
  We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges.
  
  
  CONCLUSIONS
  We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Otolaryngology, Harvard Medical School.|Center for Regenerative Medicine.|Massachusetts Eye and Ear Infirmary.|Brigham and Women's Hospital, Boston.
authors.forename: Jayme R
authors.initials: JR
authors.lastname: Dowdall
authors.affiliation: Departments of Pathology, Massachusetts General Hospital and Harvard Medical School.|Massachusetts Eye and Ear Infirmary.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.affiliation: Department of Otolaryngology, Harvard Medical School.|Massachusetts Eye and Ear Infirmary.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hartnick
authors.affiliation: Center for Regenerative Medicine.|Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vinarsky
authors.affiliation: Center for Regenerative Medicine.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mou
authors.affiliation: Center for Regenerative Medicine.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology, Harvard Medical School.|Massachusetts Eye and Ear Infirmary.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Song
authors.affiliation: Department of Otolaryngology, Harvard Medical School.|Massachusetts Eye and Ear Infirmary.
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Franco
authors.affiliation: Department of Otolaryngology, Harvard Medical School.|Center for Regenerative Medicine.|Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital.|Harvard Stem Cell Institute, Cambridge, Massachusetts, U.S.A.
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Rajagopal
mesh_terms: D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053535:Keratin-13 / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007820:Laryngeal Mucosa / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D011498:Protein Precursors / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012016:Reference Values; D014827:Vocal Cords / Q000166:cytology* / Q000378:metabolism
chemical_list: D053535:Keratin-13; D053547:Keratin-14; D019394:Ki-67 Antigen; D011498:Protein Precursors; C032253:involucrin
keywords: Vocal fold; basal cell; biomarkers; cytokeratin; differentiation; epithelium; histology; involucrin; larynx; proliferation; stratified squamous; true vocal cord