Evidence for stem-cell niches in the tracheal epithelium

It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been dem...

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Vydáno v:American journal of respiratory cell and molecular biology Ročník 24; číslo 6; s. 662
Hlavní autoři: Borthwick, D W, Shahbazian, M, Krantz, Q T, Dorin, J R, Randell, S H
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Thoracic Society 01.06.2001
Témata:
Animals
Keratins - biosynthesis
Mice
Mice, Transgenic
Regeneration
Respiratory Mucosa - cytology
Respiratory Mucosa - injuries
Respiratory Mucosa - physiology
Respiratory Mucosa - transplantation
Stem Cell Transplantation
Stem Cells - cytology
Stem Cells - physiology
Trachea - cytology
Trachea - injuries
Trachea - physiology
Trachea - transplantation
ISSN:1044-1549
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Shrnutí:It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been demonstrated in the airway. We discovered a distinct population of cells displaying high levels of keratin expression in murine tracheal submucosal gland ducts, and tested the hypothesis that bromodeoxyuridine (BrdU) label-retaining cells (LRCs), thought to represent the S-cells, were present in this compartment. Mice received weekly epithelial damage by intratracheal detergent or SO(2) inhalation for 4 wk and received intraperitoneal injections of BrdU every 48 h during the injury and repair period. At 3 and 6 d after injury, BrdU-positive epithelial cells were noted along the entire tracheal length in both basal and lumenal cell positions. At later time points (20 and 95 d) LRCs were localized to gland ducts in the upper trachea and to systematically arrayed foci in the lower trachea, typically near the cartilage-intercartilage junction. LRCs were not pulmonary neuroendocrine cells. Heterotopic tracheal grafts after surface epithelial removal demonstrated reconstitution of a surface-like epithelium from gland remnants. These results suggest that airway epithelial S cells are localized to specific niches.
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ISSN:1044-1549
DOI:10.1165/ajrcmb.24.6.4217