Document Detail

A single cell functions as a tissue-specific stem cell and the in vitro niche-forming cell.
MedLine Citation:
PMID:  21131442     Owner:  NLM     Status:  MEDLINE    
Tissue-specific stem cell (TSC) behavior is determined by the stem cell niche. However, delineation of the TSC-niche interaction requires purification of both entities. We reasoned that the niche could be defined by the location of the TSC. We demonstrate that a single CD49f(bright)/Sca1(+)/ALDH(+) basal cell generates rare label-retaining cells and abundant label-diluting cells. Label-retaining and label-diluting cells were located in the rimmed domain of a unique clone type, the rimmed clone. The TSC property of self-renewal was tested by serial passage at clonal density and analysis of clone-forming cell frequency. A single clone could be passaged up to five times and formed only rimmed clones. Thus, rimmed clone formation was a cell-intrinsic property. Differentiation potential was evaluated in air-liquid interface cultures. Homogenous cultures of rimmed clones were highly mitotic but were refractory to standard differentiation signals. However, rimmed clones that were cocultured with unfractionated tracheal cells generated each of the cell types found in the tracheal epithelium. Thus, the default niche is promitotic: Multipotential differentiation requires adaptation of the niche. Because lung TSCs are typically evaluated after injury, the behavior of CD49f(bright)/Sca1(+)/ALDH(+) cells was tested in normal and naphthalene-treated mice. These cells were mitotically active in the normal and repaired epithelium, their proliferation rate increased in response to injury, and they retained label for 34 days. We conclude that the CD49f(bright)/Sca1(+)/ALDH(+) tracheal basal cell is a TSC, that it generates its own niche in vitro, and that it participates in tracheal epithelial homeostasis and repair.
Moumita Ghosh; Karen M Helm; Russell W Smith; Matthew S Giordanengo; Bilan Li; Hongmei Shen; Susan D Reynolds
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-12-03
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  45     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-07     Completed Date:  2011-11-08     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  459-69     Citation Subset:  IM    
Department of Pediatrics, National Jewish Health Denver, CO, USA.
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MeSH Terms
Bromodeoxyuridine / pharmacology
Cell Differentiation
Cells, Cultured
Epithelial Cells / cytology
Flow Cytometry / methods
Integrin alpha6 / metabolism
Lung / cytology
Mice, Inbred C57BL
Naphthalenes / pharmacology
Stem Cells / cytology*
Trachea / cytology
Grant Support
Reg. No./Substance:
0/Integrin alpha6; 0/Naphthalenes; 2166IN72UN/naphthalene; 59-14-3/Bromodeoxyuridine

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