help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hong, K. U.
Right arrow Articles by Stripp, B. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hong, K. U.
Right arrow Articles by Stripp, B. R.

Am. J. Respir. Cell Mol. Biol., Volume 24, Number 6, June, 2001 671-681

Clara Cell Secretory Protein-Expressing Cells of the Airway Neuroepithelial Body Microenvironment Include a Label-Retaining Subset and Are Critical for Epithelial Renewal after Progenitor Cell Depletion

Kyung U. Hong,* Susan D. Reynolds,* Adam Giangreco, Cheryl M. Hurley, and Barry R. Stripp

Department of Environmental Medicine, University of Rochester, Rochester, New York

Stem cells with potential to contribute to the re-establishment of the normal bronchiolar epithelium have not been definitively demonstrated. We previously established that neuroepithelial bodies (NEBs) sequester regenerative cells that contribute to bronchiolar regeneration after selective chemical depletion of Clara cells, a major progenitor cell population. Two candidate stem cells were identified on the basis of proliferative potential after chemical ablation: a pollutant-resistant subpopulation of Clara cells that retain their expression of Clara cell secretory protein (CCSP) (variant CCSP-expressing [CE] cells or vCE cells) and calcitonin gene-related peptide (CGRP)-expressing pulmonary neuroendocrine cells (PNECs). In the present study, two populations of label-retaining cells were identified within the NEB: CGRP-expressing cells and a subpopulation of CE cells. To investigate contributions made by CE and CGRP-expressing cells to epithelial renewal, CE cells were ablated through acute administration of ganciclovir to transgenic mice expressing herpes simplex virus thymidine kinase under the regulatory control of the mouse CCSP promoter. CGRP-immunoreactive PNECs proliferated after depletion of CE cells, yet were unable to repopulate CE cell-depleted airways. These results support the notion that vCE cells represent either an airway stem cell or are critical for stem cell maintenance, and suggest that PNECs are not sufficient for epithelial renewal.

* Equally contributing authors.
Abbreviations: acetylated tubulin, ACT; basement membrane, BM; bromodeoxyuridine, BrdU; Clara-cell secretory protein, CCSP; CCSP-HSVtk, CCtk; CCSP-expressing, CE; calcitonin gene-related peptide, CGRP; cytochrome P450 2F2 isozyme, CYP2F2; 4,6-diamidino-2-phenylindole, DAPI; ganciclovir, GCV; herpes simplex virus thymidine kinase, HSVtk; immunoreactive, IR; messenger RNA, mRNA; neuroepithelial body, NEB; phosphate-buffered saline, PBS; pulmonary neuroendocrine cell, PNEC; standard error of the mean, SEM; transit-amplifying, TA; thymine deoxyribose, TdR; variant CE, vCE.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
I. De Proost, I. Pintelon, I. Brouns, A. B. A. Kroese, D. Riccardi, P. J. Kemp, J.-P. Timmermans, and D. Adriaensen
Functional Live Cell Imaging of the Pulmonary Neuroepithelial Body Microenvironment
Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 180 - 189.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop
Stem Cells and Cell Therapies in Lung Biology and Lung Diseases
Proceedings of the ATS, July 15, 2008; 5(5): 637 - 667.
[Full Text] [PDF]

Home page
 JCOHome page
C. D. Peacock and D. N. Watkins
Cancer Stem Cells and the Ontogeny of Lung Cancer
J. Clin. Oncol., June 10, 2008; 26(17): 2883 - 2889.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. Kida, M. L. Mucenski, A. R. Thitoff, T. D. Le Cras, K.-S. Park, M. Ikegami, W. Muller, and J. A. Whitsett
GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium
Am. J. Pathol., June 1, 2008; 172(6): 1542 - 1554.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
S. D. Reynolds, A. C. Zemke, A. Giangreco, B. L. Brockway, R. M. Teisanu, J. A. Drake, T. Mariani, P. Y.P. Di, M. M. Taketo, and B. R. Stripp
Conditional Stabilization of {beta}-Catenin Expands the Pool of Lung Stem Cells
Stem Cells, May 1, 2008; 26(5): 1337 - 1346.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
B. R. Stripp and S. D. Reynolds
Maintenance and Repair of the Bronchiolar Epithelium
Proceedings of the ATS, April 15, 2008; 5(3): 328 - 333.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
Y. Zhu, C. Ehre, L. H. Abdullah, J. K. Sheehan, M. Roy, C. M. Evans, B. F. Dickey, and C. W. Davis
Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways
J. Physiol., April 1, 2008; 586(7): 1977 - 1992.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. F. Kim
Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1092 - L1098.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. P. Wong, A. E. Dutly, A. Sacher, H. Lee, D. M. Hwang, M. Liu, S. Keshavjee, J. Hu, and T. K. Waddell
Targeted cell replacement with bone marrow cells for airway epithelial regeneration
Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L740 - L752.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. Summer, K. Fitzsimmons, D. Dwyer, J. Murphy, and A. Fine
Isolation of an Adult Mouse Lung Mesenchymal Progenitor Cell Population
Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 152 - 159.
[Abstract] [Full Text] [PDF]

Home page
 Brief Funct Genomic ProteomicHome page
D. Angeloni
Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease
Brief Funct Genomic Proteomic, May 24, 2007; (2007) elm007v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. D. Reynolds, H. Shen, P. R. Reynolds, T. Betsuyaku, J. M. Pilewski, F. Gambelli, M. DeGuiseppe, L. A. Ortiz, and B. R. Stripp
Molecular and functional properties of lung SP cells
Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L972 - L983.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Giangreco, K. R. Groot, and S. M. Janes
Lung Cancer and Lung Stem Cells: Strange Bedfellows?
Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 547 - 553.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
I. Kouznetsova, C. E. Chwieralski, R. Balder, M. Hinz, A. Braun, N. Krug, and W. Hoffmann
Induced Trefoil Factor Family 1 Expression by Trans-Differentiating Clara Cells in a Murine Asthma Model
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 286 - 295.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. F. Andrade, A. P. Wong, T. K. Waddell, S. Keshavjee, and M. Liu
Cell-based tissue engineering for lung regeneration
Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L510 - L518.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. L. Rawlins, L. E. Ostrowski, S. H. Randell, and B. L. M. Hogan
Inaugural Article: Lung development and repair: Contribution of the ciliated lineage
PNAS, January 9, 2007; 104(2): 410 - 417.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
R. Hajj, T. Baranek, R. Le Naour, P. Lesimple, E. Puchelle, and C. Coraux
Basal Cells of the Human Adult Airway Surface Epithelium Retain Transit-Amplifying Cell Properties
Stem Cells, January 1, 2007; 25(1): 139 - 148.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
S. H. Randell
Airway Epithelial Stem Cells and the Pathophysiology of Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2006; 3(8): 718 - 725.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
I. Nazarenko, G. Kristiansen, S. Fonfara, R. Guenther, C. Gieseler, W. Kemmner, R. Schafer, I. Petersen, and C. Sers
H-REV107-1 Stimulates Growth in Non-Small Cell Lung Carcinomas via the Activation of Mitogenic Signaling
Am. J. Pathol., October 1, 2006; 169(4): 1427 - 1439.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. J. Homer, Z. Zhu, L. Cohn, C. G. Lee, W. I. White, S. Chen, and J. A. Elias
Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation
Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L502 - L511.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
E. L. Rawlins and B. L. M. Hogan
Epithelial stem cells of the lung: privileged few or opportunities for many?
Development, July 1, 2006; 133(13): 2455 - 2465.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T.-Y. Ling, M.-D. Kuo, C.-L. Li, A. L. Yu, Y.-H. Huang, T.-J. Wu, Y.-C. Lin, S.-H. Chen, and J. Yu
Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro
PNAS, June 20, 2006; 103(25): 9530 - 9535.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. R. Stripp and S. D. Shapiro
Stem Cells in Lung Disease, Repair, and the Potential for Therapeutic Interventions: State-of-the-Art and Future Challenges.
Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 517 - 522.
[Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
D. J. Weiss, M. A. Berberich, Z. Borok, D. B. Gail, J. K. Kolls, C. Penland, and D. J. Prockop
Adult Stem Cells, Lung Biology, and Lung Disease
Proceedings of the ATS, May 1, 2006; 3(3): 193 - 207.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K.-S. Park, J. M. Wells, A. M. Zorn, S. E. Wert, V. E. Laubach, L. G. Fernandez, and J. A. Whitsett
Transdifferentiation of Ciliated Cells during Repair of the Respiratory Epithelium
Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 151 - 157.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H. Chang, L. W. Chang, Y.-H. Cheng, W.-T. Tsai, M.-X. Tsai, and P. Lin
Preferential Induction of CYP1A1 and CYP1B1 in CCSP-Positive Cells
Toxicol. Sci., January 1, 2006; 89(1): 205 - 213.
[Abstract] [Full Text] [PDF]

Home page
 ERRHome page
C. Coraux, R. Hajj, P. Lesimple, and E. Puchelle
In vivo models of human airway epithelium repair and regeneration
Eur. Respir. Rev., December 1, 2005; 14(97): 131 - 136.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Kim, A. J. Schein, and J. A. Nadel
E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells
Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L1049 - L1060.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A.-K. T. Perl, S. E. Wert, D. E. Loudy, Z. Shan, P. A. Blair, and J. A. Whitsett
Conditional Recombination Reveals Distinct Subsets of Epithelial Cells in Trachea, Bronchi, and Alveoli
Am. J. Respir. Cell Mol. Biol., November 1, 2005; 33(5): 455 - 462.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. A. Voynow, B. M. Fischer, B. C. Roberts, and A. D. Proia
Basal-like Cells Constitute the Proliferating Cell Population in Cystic Fibrosis Airways
Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 1013 - 1018.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
S. M. Majka, M. A. Beutz, M. Hagen, A. A. Izzo, N. Voelkel, and K. M. Helm
Identification of Novel Resident Pulmonary Stem Cells: Form and Function of the Lung Side Population
Stem Cells, September 1, 2005; 23(8): 1073 - 1081.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
R. Meuwissen and A. Berns
Mouse models for human lung cancer
Genes & Dev., March 15, 2005; 19(6): 643 - 664.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. R. Stripp and S. D. Reynolds
Bioengineered Lung Epithelium: Implications for Basic and Applied Studies in Lung Tissue Regeneration
Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 85 - 86.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. Coraux, B. Nawrocki-Raby, J. Hinnrasky, C. Kileztky, D. Gaillard, C. Dani, and E. Puchelle
Embryonic Stem Cells Generate Airway Epithelial Tissue
Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 87 - 92.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. D. Reynolds, A. Giangreco, K. U. Hong, K. E. McGrath, L. A. Ortiz, and B. R. Stripp
Airway injury in lung disease pathophysiology: selective depletion of airway stem and progenitor cell pools potentiates lung inflammation and alveolar dysfunction
Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1256 - L1265.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. R. Pitt and L. A. Ortiz
Stem cells in lung biology
Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L621 - L623.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Giangreco, H. Shen, S. D. Reynolds, and B. R. Stripp
Molecular phenotype of airway side population cells
Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L624 - L630.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. G. Schoch, A. Lori, K. A. Burns, T. Eldred, J. C. Olsen, and S. H. Randell
A subset of mouse tracheal epithelial basal cells generates large colonies in vitro
Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L631 - L642.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. U. Hong, S. D. Reynolds, S. Watkins, E. Fuchs, and B. R. Stripp
In vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations
Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L643 - L649.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. U. Hong, S. D. Reynolds, S. Watkins, E. Fuchs, and B. R. Stripp
Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium
Am. J. Pathol., February 1, 2004; 164(2): 577 - 588.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Maeshima, S. Yamashita, and Y. Nojima
Identification of Renal Progenitor-Like Tubular Cells that Participate in the Regeneration Processes of the Kidney
J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3138 - 3146.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
J. Pan, H. Yeger, and E. Cutz
Neuronal Developmental Marker FORSE-1 Identifies a Putative Progenitor of the Pulmonary Neuroendocrine Cell Lineage During Lung Development
J. Histochem. Cytochem., December 1, 2002; 50(12): 1567 - 1578.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. D. Reynolds, P. R. Reynolds, G. S. Pryhuber, J. D. Finder, and B. R. Stripp
Secretoglobins SCGB3A1 and SCGB3A2 Define Secretory Cell Subsets in Mouse and Human Airways
Am. J. Respir. Crit. Care Med., December 1, 2002; 166(11): 1498 - 1509.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Y. You, E. J. Richer, T. Huang, and S. L. Brody
Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population
Am J Physiol Lung Cell Mol Physiol, December 1, 2002; 283(6): L1315 - L1321.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
H. Fehrenbach, A. Fehrenbach, T. Pan, M. Kasper, and R.J. Mason
Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cells in vivo
Eur. Respir. J., November 1, 2002; 20(5): 1185 - 1197.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. Pan, C. Bear, S. Farragher, E. Cutz, and H. Yeger
Cystic Fibrosis Transmembrane Conductance Regulator Modulates Neurosecretory Function in Pulmonary Neuroendocrine Cell-Related Tumor Cell Line Models
Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 553 - 560.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
A. Giangreco, S. D. Reynolds, and B. R. Stripp
Terminal Bronchioles Harbor a Unique Airway Stem Cell Population That Localizes to the Bronchoalveolar Duct Junction
Am. J. Pathol., July 1, 2002; 161(1): 173 - 182.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. F. Engelhardt
Stem Cell Niches in the Mouse Airway
Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 649 - 652.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2001 American Thoracic Society.