The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration
Open accessAbstract
Lung injury activates specialized adult epithelial progenitors to regenerate the epithelium. Depending on the extent of injury, both remaining alveolar type II cells (AEC2s) and distal airway stem/progenitors mobilize to cover denuded alveoli and restore normal barriers. The major source of airway stem/progenitors other than basal-like cells remains uncertain. Here, we define a distinct subpopulation (∼5%) of club-like lineage-negative epithelial progenitors (LNEPs) marked by high H2-K1 expression critical for alveolar repair. Quiescent H2-K1 high cells account for virtually all in vitro regenerative activity of airway lineages. After bleomycin injury, H2-K1 cells expand and differentiate in vivo to alveolar lineages. However, injured H2-K1 cells eventually develop impaired self-renewal with features of senescence, limiting complete repair. Normal H2-K1 high cells transplanted into injured lungs differentiate into alveolar cells and rescue lung function. These findings indicate that small subpopulations of specialized stem/progenitors are required for effective lung regeneration and are a potential therapeutic adjunct after major lung injury.
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
“Senescence-mediated loss of progenitor cell capabilities among AT2 and basal cell populations has been implicated in the impaired reepithelialization of damaged alveoli and airways (62).”
From Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 (2021) · cites this paper as [62]
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
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
La Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M. E., Lönnerberg, P., Furlan, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0414-6 · Cited by 4,118
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491
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
Type 2 alveolar cells are stem cells in adult lung
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. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68782 · Cited by 1,776 · cited 5×
“In the injured lung parenchyma, both remaining type II cells (AEC2s) and stem/progenitors emanating from distal airways contribute importantly to alveolar repair (Barkauskas et al., 2013; Kumar et al., 2011; McQualter, 2019; Zacharias et al., 2018; Zheng et al., 2017).”
BackgroundMethodInfluentialRelaix, F., & Zammit, P. S. (2012) · Development · doi:10.1242/dev.069088 · Cited by 888
Hogan, B. L. M., Barkauskas, C. E., Chapman, H. A., Epstein, J. A., Jain, R., Hsia, C. C. W., Niklason, L., Calle, E., Le, A., Randell, S. H., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.07.012 · Cited by 876
Self-citationRawlins, E. L., Okubo, T., Xue, Y., Brass, D. M., Auten, R. L., Hasegawa, H., Wang, F., & Hogan, B. L. M. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.04.002 · Cited by 872
Cited by
Sorted by citations
Strunz, M., Simon, L. M., Ansari, M., Kathiriya, J. J., Angelidis, I., Mayr, C. H., Tsidiridis, G., Lange, M., Mattner, L. F., Yee, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17358-3 · Cited by 740
Self-citationProgenitor identification and SARS-CoV-2 infection in human distal lung organoids
Salahudeen, A. A., Choi, S. S., Rustagi, A., Zhu, J., van Unen, V., de la O, S. M., Flynn, R. A., Margalef-Català, M., Santos, A. J. M., Ju, J., et al. (2020) · Nature · doi:10.1038/s41586-020-3014-1 · Cited by 416
The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future
Basil, M. C., Katzen, J., Engler, A. E., Guo, M., Herriges, M. J., Kathiriya, J. J., Windmueller, R., Ysasi, A. B., Zacharias, W. J., Chapman, H. A., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.03.009 · Cited by 414
Self-citationInfluenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract
Flerlage, T., Boyd, D. F., Meliopoulos, V., Thomas, P. G., & Schultz‐Cherry, S. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00542-7 · Cited by 419
Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells
Kathiriya, J. J., Wang, C., Zhou, M., Brumwell, A. N., Cassandras, M., Saux, C. J. L., Cohen, M., Alysandratos, K., Wang, B., Wolters, P. J., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00809-4 · Cited by 273
Self-citation
Metadata
- Authors
- Kathiriya, J. J., Brumwell, A. N., Jackson, J. R., Tang, X., & Chapman, H. A.
- Affiliations
- University of California, San Francisco (US)
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Chapman, Harold A.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 26
- Issue
- 3
- Pages
- 346-358.e4
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC7233183
- OpenAlex
- W3002314962
- Cited by
- 246
- References
- 46
- Citations by year
- 2026: 26 · 2025: 38 · 2024: 42 · 2023: 48 · 2022: 33 · 2021: 33 · 2020: 26
- FWCI
- 19.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- Clara cells, alveolar regeneration, lung injury, alveolar type II cells, epithelial progenitors, cellular senescence, self-renewal, cell transplantation
- MeSH terms
- Cell Differentiation, Epithelial Cells, Humans, Lung, Stem Cells, Lung Injury, Alveolar Epithelial Cells
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
