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Tissue-Specific Stem Cells
Article first published online: 2 MAR 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 3, pages 623–633, March 2009
How to Cite
McQualter, J. L., Brouard, N., Williams, B., Baird, B. N., Sims-Lucas, S., Yuen, K., Nilsson, S. K., Simmons, P. J. and Bertoncello, I. (2009), Endogenous Fibroblastic Progenitor Cells in the Adult Mouse Lung Are Highly Enriched in the Sca-1 Positive Cell Fraction. STEM CELLS, 27: 623–633. doi: 10.1634/stemcells.2008-0866
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: J.L.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; N.B.: conception and design, collection and/or assembly of data, data analysis and interpretation; B.W.: collection and/or assembly of data; B.N.B.: collection and/or assembly of data; S.S.-L.: collection and/or assembly of data; K.Y.: collection and/or assembly of data; S.K.N.: collection and/or assembly of data; P.J.S.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation; I.B.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript.
First published online in STEM CELLSExpress December 11, 2008.
- Issue published online: 2 MAR 2009
- Article first published online: 2 MAR 2009
- Manuscript Accepted: 11 DEC 2008
- Manuscript Received: 1 SEP 2008
- Adult stem cells;
- Mesenchymal stem cells;
- Stromal cells;
- Tissue-specific stem cells
Originally identified as a marker specifying murine hematopoietic stem cells, the Sca-1 antigen has since been shown to be differentially expressed by candidate stem cells in tissues including vascular endothelium, skeletal muscle, mammary gland, and prostate of adult mice. In the adult murine lung, Sca-1 has previously been identified as a selectable marker for the isolation of candidate nonhematopoietic (CD45−), nonendothelial (CD31−) bronchioalveolar stem cells (BASC) located at the bronchioalveolar duct junction that coexpress surfactant protein C and the Clara cell specific protein. Our systematic analysis of CD45−CD31−Sca-1+ cells in fetal, neonatal, and adult lung shows that very few of these cells are detectable prior to birth but expand exponentially postnatally coinciding with the transition from the saccular to the alveolar stage of lung development. Unlike candidate BASCs, the CD45−CD31−Sca-1+CD34+ cell fraction we describe coexpresses immunophenotypic markers (Thy-1 and platelet-derived growth factor receptor α) that define lung fibroblastic rather than epithelial cells. The mesenchymal “signature” of the CD45−CD31−Sca-1+CD34+ cell fraction is further confirmed by transcriptional profiling, by cell culture studies demonstrating enrichment for clonogenic lipofibroblastic and nonlipofibroblastic progenitors, and by immunohistochemical localization of Sca-1 in perivascular cells of the lung parenchyma. Although the CD45−CD31−Sca-1+CD34+ cell phenotype does define endogenous clonogenic progenitor cells in the adult murine lung, our data indicate that these progenitors are predominantly representative of mesenchymal cell lineages, and highlights the pressing need for the identification of alternative markers and robust functional assays for the identification and characterization of epithelial and fibroblastic stem and progenitor cell populations in the adult lung. STEM CELLS2009;27:623–633