Document Detail


Multidirectional differentiation of Achaete-Scute homologue-1-defined progenitors in lung development and injury repair.
MedLine Citation:
PMID:  22878413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple cells contribute to the function of lungs. Pulmonary neuroendocrine cells (PNECs) are important for the regulation of breathing and carcinogenesis, although they represent only a small population of the airway lining. Achaete-Scute homologue-1 (Ascl1), a proneural basic helix-loop-helix transcription factor, is critical for the development of PNECs. We postulated that Ascl1-defined cells (ASDCs) may be progenitors, and traced their fate during development and injury repair. R26R-stop-lacZ (Rosa) reporter mice were crossed with Ascl1-Cre or Ascl1-CreERTM mice, in which the Ascl1 promoter drives the expression of Cre or inducible Cre recombinase, respectively. ASDCs and their descendants will be permanently labeled. The labeled cells were characterized by immunohistochemistry, using highly specific differentiation markers. Lineage studies revealed a population that proliferates before the pseudoglandular stage, and widely contributes to different compartments. When ASDCs were labeled on Embryonic Day 9.5, they gave rise to both airway and alveolar cells, but when labeled on Embryonic Day 11.5, they only gave rise to airway cells. In postnatal naphthalene injury, ASDCs contributed to regenerating Clara cells. In conclusion, Ascl1-defined cells in the lung represent a novel multipotent lineage, indicating a close relationship of neuroendocrine cells with other cell types.
Authors:
Yan Li; R Ilona Linnoila
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-08-09
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  47     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-01-25     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  768-75     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acute Lung Injury / chemically induced,  pathology*,  physiopathology
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism*
Cell Differentiation*
Epithelial Cells / metabolism,  physiology
Female
Gene Expression
Lung / embryology,  pathology*
Male
Mice
Mice, Transgenic
Naphthalenes
Neuroendocrine Cells / metabolism,  physiology
Regeneration
Statistics, Nonparametric
Stem Cells / metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Ascl1 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Naphthalenes; 2166IN72UN/naphthalene
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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