The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Type 2 alveolar cells are stem cells in adult lung
Open accessAbstract
Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells. Moreover, if many AEC2s were specifically ablated, high-resolution imaging of intact lungs showed that individual survivors undergo rapid clonal expansion and daughter cell dispersal. Individual lineage-labeled AEC2s placed into 3D culture gave rise to self-renewing "alveolospheres," which contained both AEC2s and cells expressing multiple AEC1 markers, including HOPX, a new marker for AEC1s. Growth and differentiation of the alveolospheres occurred most readily when cocultured with primary PDGFRα⁺ lung stromal cells. This population included lipofibroblasts that normally reside close to AEC2s and may therefore contribute to a stem cell niche in the murine lung. Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“or require the presence of a mesenchymal feeder layer (Barkauskas et al., 2013)”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Barkauskas et al., 2013
In the citing paper
“and can differentiate into alveolar epithelial type 1 (AEC1) cells.”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Barkauskas et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Raghu, G., Collard, H. R., Egan, J. J., Martinez, F. J., Behr, J., Brown, K. K., Colby, T. V., Cordier, J.-F., Flaherty, K. R., Lasky, J. A., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2009-040gl · Cited by 7,186
Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer
Kim, C. F. B., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., Crowley, D. G., Bronson, R. T., & Jacks, T. (2005) · Cell · doi:10.1016/j.cell.2005.03.032 · Cited by 2,229
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Basal cells as stem cells of the mouse trachea and human airway epithelium
Rock, J. R., Onaitis, M. W., Rawlins, E. L., Lu, Y., Clark, C. P., Xue, Y., Randell, S. H., & Hogan, B. L. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906850106 · Cited by 1,591
Self-citationLgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro
Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2009.11.013 · Cited by 1,547
Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain
Hama, H., Kurokawa, H., Kawano, H., Ando, R., Shimogori, T., Noda, H., Fukami, K., Sakaue-Sawano, A., & Miyawaki, A. (2011) · Nature Neuroscience · doi:10.1038/nn.2928 · Cited by 1,154
Rock, J. R., Barkauskas, C. E., Cronce, M. J., Xue, Y., Harris, J. R., Liang, J., Noble, P. W., & Hogan, B. L. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117988108 · Cited by 1,048
Self-citationIntestinal Stem Cell Replacement Follows a Pattern of Neutral Drift
López‐García, C., Klein, A. M., Simons, B. D., & Winton, D. J. (2010) · Science · doi:10.1126/science.1196236 · Cited by 660
Distinct contribution of stem and progenitor cells to epidermal maintenance
Mascré, G., Dekoninck, S., Drogat, B., Youssef, K. K., Brohée, S., Sotiropoulou, P. A., Simons, B. D., & Blanpain, C. (2012) · Nature · doi:10.1038/nature11393 · Cited by 586
Kumar, P., Hu, Y., Yamamoto, Y., Hoe, N. B., Wei, T. S., Mu, D., Sun, Y., Lim, S. J., Dagher, R., Zielonka, E. M., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.001 · Cited by 578
Alveolar Cell Senescence in Patients with Pulmonary Emphysema
Tsuji, T., Aoshiba, K., & Nagai, A. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200509-1374oc · Cited by 527
Targeted Injury of Type II Alveolar Epithelial Cells Induces Pulmonary Fibrosis
Sisson, T. H., Mendez, M. P., Choi, K., Subbotina, N., Courey, A. J., Cunningham, A. K., Dave, A., Engelhardt, J. F., Liu, X., White, E. S., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200810-1615oc · Cited by 483
Evolutionary Divergence of Platelet-Derived Growth Factor Alpha Receptor Signaling Mechanisms
Hamilton, T., Klinghoffer, R. A., Corrin, P. D., & Soriano, P. M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.11.4013-4025.2003 · Cited by 435
Renewal of alveolar epithelium in the rat following exposure to NO2.
Evans, M. J., Cabral, L. J., Stephens, R. J., & Freeman, G. (1973) · PubMed Central · Cited by 427
Kapançi, Y., Weibel, E. R., Kaplan, H. P., & Robinson, F. (1969) · PubMed · Cited by 418
Chapman, H. A., Li, X., Alexander, J. P., Brumwell, A. N., Lorizio, W., Tan, K., Sonnenberg, A., Wei, Y., & Vu, T. H. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57673 · Cited by 407
Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung
McQualter, J. L., Yuen, K., Williams, B., & Bertoncello, I. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909207107 · Cited by 386
Mitamura, T., Higashiyama, S., Taniguchi, N., Klagsbrun, M., & Mekada, E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1015 · Cited by 312
Lu, C. P., Polak, L., Rocha, A. S., Pasolli, H. A., Chen, S.-C., Sharma, N., Blanpain, C., & Fuchs, E. (2012) · Cell · doi:10.1016/j.cell.2012.04.045 · Cited by 301
Hop Is an Unusual Homeobox Gene that Modulates Cardiac Development
Chen, F., Kook, H. Y., Milewski, R. C. K., Gitler, A. D., Lu, M. M., Li, J., Nazarian, R., Schnepp, R. W., Jen, K., Biben, C., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)00932-7 · Cited by 289
Evidence for Adult Lung Growth in Humans
Butler, J. P., Loring, S. H., Patz, S., Tsuda, A., Yablonskiy, D. A., & Mentzer, S. J. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203983 · Cited by 277
Monitoring of collagen and collagen fragments in chromatography of protein mixtures
Huszar, G. B., Maiocco, J., & Naftolin, F. N. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90481-9 · Cited by 265
Leeman, K. T., Leder, E., Aslam, M., Lau, A. N., Raiser, D. M., Lee, J., Balasubramaniam, V., Fredenburgh, L. E., Mitsialis, S. A., Kourembanas, S., et al. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00347.2011 · Cited by 239
THE PULMONARY LIPOFIBROBLAST (LIPID INTERSTITIAL CELL) AND ITS CONTRIBUTIONS TO ALVEOLAR DEVELOPMENT
McGowan, S. E., & Torday, J. S. (1997) · Annual Review of Physiology · doi:10.1146/annurev.physiol.59.1.43 · Cited by 215
Thaloor, D., Miller, K. J., Gephart, J., Mitchell, P. O., & Pavlath, G. K. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.277.2.c320 · Cited by 211
Anisimov, V. N. (1982) · Experimental Pathology · doi:10.1016/s0232-1513(82)80001-7 · Cited by 199
Chen, H., Matsumoto, K., Brockway, B., Rackley, C. R., Liang, J., Lee, J., Jiang, D., Noble, P. W., Randell, S. H., Kim, C. F., et al. (2012) · Stem Cells · doi:10.1002/stem.1150 · Cited by 192
Self-citationProgress Toward Improving Animal Models for Idiopathic Pulmonary Fibrosis
Degryse, A. L., & Lawson, W. E. (2011) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31821aa000 · Cited by 162
Chen, L., Acciani, T. H., Cras, T. D. L., Lutzko, C., & Perl, A. T. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0030oc · Cited by 145
Definitions, Epidemiology, Pathophysiology, Diagnosis, and Staging
(1995) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm/152.5_pt_2.s78 · Cited by 142
Boström, H., Gritli-Linde, A., & Betsholtz, C. (2001) · Developmental Dynamics · doi:10.1002/dvdy.1225 · Cited by 140
Senescence Hypothesis for the Pathogenetic Mechanism of Chronic Obstructive Pulmonary Disease
Aoshiba, K., & Nagai, A. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200904-017rm · Cited by 130
Primary Epithelial Cell Models for Cystic Fibrosis Research
Randell, S. H., Fulcher, M. L., O’Neal, W. K., & Olsen, J. C. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-120-8_18 · Cited by 129
Self-citationMolecular Mechanisms in Progressive Idiopathic Pulmonary Fibrosis
Steele, M. P., & Schwartz, D. A. (2012) · Annual Review of Medicine · doi:10.1146/annurev-med-042711-142004 · Cited by 126
Vasilescu, D. M., Gao, Z., Saha, P. K., Yin, L., Wang, G., Haefeli‐Bleuer, B., Ochs, M., Weibel, E. R., & Hoffman, E. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215112109 · Cited by 118
Alveolar Dynamics during Respiration
Namati, E., Thiesse, J., Sieren, J. C., & McLennan, G. (2007) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0120oc · Cited by 112
HTII-280, a Biomarker Specific to the Apical Plasma Membrane of Human Lung Alveolar Type II Cells
Gonzalez, R. F., Allen, L., Gonzales, L. W., Ballard, P. L., & Dobbs, L. G. (2010) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2010.956433 · Cited by 110
Stem cells of the adult lung: their development and role in homeostasis, regeneration, and disease
Wansleeben, C., Barkauskas, C. E., Rock, J. R., & Hogan, B. L. M. (2012) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.58 · Cited by 108
Self-citationZheng, D., Limmon, G. V., Yin, L., Leung, N. H. N., Yu, H., Chow, V. T. K., & Chen, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048451 · Cited by 96
Functional Analysis of Two Distinct Bronchiolar Progenitors during Lung Injury and Repair
Teisanu, R. M., Chen, H., Matsumoto, K., McQualter, J. L., Potts, E. N., Foster, W. M., Bertoncello, I., & Stripp, B. R. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2010-0098oc · Cited by 95
Self-citationYin, Z., Gonzales, L. W., Kolla, V., Rath, N., Zhang, Y., Lu, M. M., Kimura, S., Ballard, P. L., Beers, M. F., Epstein, J. A., et al. (2006) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00385.2005 · Cited by 83
Salaun, B., de Saint-Vis, B., Pacheco, N., Pachéco, Y., Riesler, A., Isaac, S., Leroux, C., Clair‐Moninot, V., Pin, J., Griffith, J. M., et al. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63174-4 · Cited by 83
Alveolar Epithelial Type II Cells Induce T Cell Tolerance to Specific Antigen
Lo, B., Hansen, S., Evans, K. S., Heath, J. K., & Wright, J. R. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.2.881 · Cited by 80
Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro
Gonzalez, R. F., Allen, L., & Dobbs, L. G. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.90389.2008 · Cited by 79
The lipid interstitial cell of the pulmonary alveolus. Age and species differences.
Kaplan, N. B., Grant, M. M., & Brody, J. S. (1985) · PubMed · doi:10.1164/arrd.1985.132.6.1307 · Cited by 64
Lee, J., Kim, J., Gludish, D. W., Roach, R. R., Saunders, A., Barrios, J., Woo, A. J., Chen, H., Conner, D. A., Fujiwara, Y., et al. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0403oc · Cited by 57
Self-citationPores of Kohn are filled in normal lungs: low-temperature scanning electron microscopy
Bastacky, J., & Goerke, J. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.73.1.88 · Cited by 48
Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis
Qunn, L., Takemura, T., Ikushima, S., Ando, T., Yanagawa, T., Akiyama, O., Oritsu, M., Tanaka, N., & Kuroki, T. (2002) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-002-0618-9 · Cited by 48
Mechanical ventilation of rat lung: effect on surfactant forms
Savov, J. D., Silbajoris, R. A., & Young, S. L. (1999) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1999.277.2.l320 · Cited by 23
Flagged first, then by citations
Research works printed but not linked: 5
- Kauffman, 1980, Int Rev Exp Pathol., 22, 131
- Kapanci, 1969, Lab Invest., 20, 101
- Evans, 1973, Am J Pathol., 70, 175
- Murphy JR Corynebacterium diphtheriae. In: Baron S, ed. Medical Microbiology. 4th ed. Galveston, Texas, USA: University of Texas Medical Branch at Galveston; 1996 Chapter 32
- Kaplan, 1985, Am Rev Respir Dis., 132, 1307
Cited by
Sorted by citations
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196
“Having said this, these alveolosphere culture conditions are as yet not fully defined, requiring co-culture with non-epithelial cells (e.g., mouse lung fibroblasts) (Barkauskas et al., 2013; Jain et al., 2015).”
BackgroundNon-small-cell lung cancers: a heterogeneous set of diseases
Chen, Z., Brainson, C. F., Hammerman, P. S., Kim, C. F., & Wong, K. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3775 · Cited by 1,973
Single-cell transcriptional diversity is a hallmark of developmental potential
Gulati, G. S., Sikandar, S. S., Wesche, D. J., Manjunath, A., Bharadwaj, A., Berger, M. J., Ilagan, F., Kuo, A. H., Hsieh, R. W., Cai, S., et al. (2020) · Science · doi:10.1126/science.aax0249 · Cited by 1,571
The pivotal link between ACE2 deficiency and SARS-CoV-2 infection
Verdecchia, P., Cavallini, C., Spanevello, A., & Angeli, F. (2020) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2020.04.037 · Cited by 1,237
“[52] Therefore, the damage of pneumocytes type II due to the binding of coronavirus to ACE2 receptors is devastating for at least three reasons: 1) local unopposed ACE→Angiotensin II→AT1 receptor axis over-activity; 2) reduced production of alveolar surfactant by injured pneumocytes type II leading to reduced lung ela…”
Progress and potential in organoid research
Rossi, G., Manfrin, A., & Lutolf, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0051-9 · Cited by 1,182
Metadata
- Authors
- Barkauskas, C. E., Cronce, M. J., Rackley, C. R., Bowie, E. J., Keene, D. R., Stripp, B. R., Randell, S. H., Noble, P. W., & Hogan, B. L. M.
- Affiliations
- Duke University (US)
- Shriners Hospitals for Children (US)
- Cedars-Sinai Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2013-06-10
- Volume
- 123
- Issue
- 7
- Pages
- 3025-3036
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3696553
- OpenAlex
- W2050308681
- Cited by
- 1,776
- References
- 49
- Citations by year
- 2026: 126 · 2025: 167 · 2024: 167 · 2023: 179 · 2022: 193 · 2021: 207 · 2020: 181 · 2019: 121 · 2018: 109 · 2017: 99 · 2016: 74 · 2015: 78 · 2014: 60 · 2013: 12
- FWCI
- 60.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Heart, Lung, and Blood Institute (P01HL108793, T32HL007538, R37HL071303, U01HL111018, R01HL060539, T32HL098099, UO1HL111018)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- alveolar stem cells, lung regeneration, alveolar repair, clonal lineage tracing, surfactant protein C, self-renewal, clonal expansion, HOPX, lipofibroblasts, stem cell niche, lung injury
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Lung, Mice, Inbred C57BL, Mice, Transgenic, Stromal Cells, Coculture Techniques, Cell Lineage, Receptor, Platelet-Derived Growth Factor alpha, Cell Proliferation, Mice, Adult Stem Cells, Stem Cell Niche, Lung Injury, Alveolar Epithelial Cells, Mice, 129 Strain
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
