Tissue-Specific Stem Cells
Article first published online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1948–1960, September 2012
How to Cite
Chen, H., Matsumoto, K., Brockway, B. L., Rackley, C. R., Liang, J., Lee, J.-H., Jiang, D., Noble, P. W., Randell, S. H., Kim, C. F. and Stripp, B. R. (2012), Airway Epithelial Progenitors Are Region Specific and Show Differential Responses to Bleomycin-Induced Lung Injury. STEM CELLS, 30: 1948–1960. doi: 10.1002/stem.1150
Author contributions: C.H., M.K., and S.B.R.: conception and design; S.B.R.: financial support; S.B.R.: provision of study material or patients; C.H., M.K., B.B.L., L.J., and S.B.R.: collection and/or assembly of data; C.H., M.K., R.C.R., B.B.L., K.C.F., L.J.H., and S.B.R.: data analysis and interpretation; C.H., M.K., R.C.R., J.D., N.P.W., R.S.H., K.C.F., and S.B.R.: manuscript writing; S.B.R.: final approval of manuscript. H.C. and K.M. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 13, 2012.
- Issue published online: 20 AUG 2012
- Article first published online: 20 AUG 2012
- Accepted manuscript online: 13 JUN 2012 02:41PM EST
- Manuscript Accepted: 30 MAY 2012
- Manuscript Received: 27 FEB 2012
- NHLBI. Grant Numbers: 1U01HL099997-01, RO1 HL090136, U01 HL100402, HL064888, HL090146, HL089141
Mechanisms that regulate regional epithelial cell diversity and pathologic remodeling in airways are poorly understood. We hypothesized that regional differences in cell composition and injury-related tissue remodeling result from the type and composition of local progenitors. We used surface markers and the spatial expression pattern of an SFTPC-GFP transgene to subset epithelial progenitors by airway region. Green fluorescent protein (GFP) expression ranged from undetectable to high in a proximal-to-distal gradient. GFPhi cells were subdivided by CD24 staining into alveolar (CD24neg) and conducting airway (CD24low) populations. This allowed for the segregation of three types of progenitors displaying distinct clonal behavior in vitro. GFPneg and GFPlow progenitors both yielded lumen containing colonies but displayed transcriptomes reflective of pseudostratified and distal conducting airways, respectively. CD24lowGFPhi progenitors were present in an overlapping distribution with GFPlow progenitors in distal airways, yet expressed lower levels of Sox2 and expanded in culture to yield undifferentiated self-renewing progeny. Colony-forming ability was reduced for each progenitor cell type after in vivo bleomycin exposure, but only CD24lowGFPhi progenitors showed robust expansion during tissue remodeling. These data reveal intrinsic differences in the properties of regional progenitors and suggest that their unique responses to tissue damage drive local tissue remodeling. Stem Cells2012;30:1948–1960