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.
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
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?
Senescence-mediated loss of progenitor cell capabilities among AT2 and basal cell populations has been implicated in impaired reepithelialization of damaged alveoli and airways.
“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.
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 2,196 · see citing works
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× · see citing works
“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 · see citing works
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 · see citing works
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 855 · see citing works
Cells keep a memory of their tissue origin during axolotl limb regeneration
Kragl, M., Knapp, D., Nacu, E., Khattak, S., Maden, M., Epperlein, H. H., & Tanaka, E. M. (2009) · Nature · doi:10.1038/nature08152 · Cited by 854 · see citing works
Sox2+ Adult Stem and Progenitor Cells Are Important for Tissue Regeneration and Survival of Mice
Arnold, K., Sarkar, A., Yram, M. A., Polo, J. M., Bronson, R. T., Sengupta, S., Seandel, M., Geijsen, N., & Hochedlinger, K. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.09.001 · Cited by 754 · see citing works
Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor
Zacharias, W. J., Frank, D. B., Zepp, J. A., Morley, M. P., Alkhaleel, F. A., Kong, J., Zhou, S., Cantu, E., & Morrisey, E. E. (2018) · Nature · doi:10.1038/nature25786 · Cited by 742 · see citing works
Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells
Nabhan, A. N., Brownfield, D., Harbury, P. B., Krasnow, M. A., & Desai, T. (2018) · Science · doi:10.1126/science.aam6603 · Cited by 731 · see citing works
Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury
Vaughan, A. E., Brumwell, A. N., Xi, Y., Gotts, J. E., Brownfield, D., Treutlein, B., Tan, K., Tan, V. M., Liu, F. C., Looney, M. R., et al. (2014) · Nature · doi:10.1038/nature14112 · Cited by 662 · see citing works
Self-citationDedifferentiation of committed epithelial cells into stem cells in vivo
Tata, P. R., Mou, H., Pardo–Saganta, A., Zhao, R., Prabhu, M., Law, B. M., Vinarsky, V., Cho, J. L., Breton, S., Sahay, A., et al. (2013) · Nature · doi:10.1038/nature12777 · Cited by 657 · see citing works
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 · see citing works
p63+Krt5+ distal airway stem cells are essential for lung regeneration
Zuo, W., Zhang, T., Wu, D. Z., Guan, S. P., Liew, A.-A., Yamamoto, Y., Wang, X., Lim, S. J., Vincent, M., Lessard, M. D., et al. (2014) · Nature · doi:10.1038/nature13903 · Cited by 525 · see citing works
You, Y., Richer, E. J., Huang, T., & Brody, S. L. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00169.2002 · Cited by 442 · see citing works
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 · see citing works
Self-citationPlasticity and reprogramming of differentiated cells in amphibian regeneration
Brockes, J. P., & Kumar, A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm881 · Cited by 405 · see citing works
Regeneration of Male Germline Stem Cells by Spermatogonial Dedifferentiation in Vivo
Brawley, C. M., & Matunis, E. L. (2004) · Science · doi:10.1126/science.1097676 · Cited by 402 · see citing works
Observation of Antigen-Dependent CD8+ T-Cell/ Dendritic Cell Interactions in Vivo
Schaefer, B. C., Schaefer, M. L., Kappler, J. W., Marrack, P., & Kedl, R. M. (2001) · Cellular Immunology · doi:10.1006/cimm.2001.1895 · Cited by 394 · see citing works
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 · see citing works
Single-Cell Transcriptomics Meets Lineage Tracing
Kester, L., & van Oudenaarden, A. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.014 · Cited by 375 · see citing works
Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6
Lee, J., Tammela, T., Hofree, M., Choi, J., Marjanovic, N. D., Han, S., Canner, D. A., Wu, K., Paschini, M., Bhang, D. H., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.028 · Cited by 362 · see citing works
Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries
Kai, T., & Spradling, A. C. (2004) · Nature · doi:10.1038/nature02436 · Cited by 344 · see citing works
Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction
Liu, Q., Liu, K., Cui, G., Huang, X., Yao, S., Guo, W., Qin, Z., Li, Y., Yang, R., Pu, W., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0346-6 · Cited by 320 · see citing works
Local lung hypoxia determines epithelial fate decisions during alveolar regeneration
Xi, Y., Kim, T., Brumwell, A. N., Driver, I. H., Wei, Y., Tan, V. M., Jackson, J., Xu, J., Lee, D.-K., Gotts, J. E., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3580 · Cited by 268 · see citing works
Self-citationBronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo
Salwig, I., Spitznagel, B., Vazquez‐Armendariz, A. I., Khalooghi, K., Günther, S., Herold, S., Szibor, M., & Braun, T. W. (2019) · The EMBO Journal · doi:10.15252/embj.2019102099 · Cited by 192 · see citing works
Yang, Y., Riccio, P. N., Schotsaert, M., Mori, M., Lü, J., Lee, D.-K., García‐Sastre, A., Xu, J., & Cardoso, W. V. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.03.001 · Cited by 191 · see citing works
Quantius, J., Schmoldt, C., Vazquez‐Armendariz, A. I., Becker, C., Agha, E. E., Wilhelm, J., Morty, R. E., Vadász, I., Mayer, K., Gattenloehner, S., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005544 · Cited by 121 · see citing works
Influenza virus and cell signaling pathways
Gaur, P., Munjhal, A., & Lal, S. K. (2011) · Medical Science Monitor · doi:10.12659/msm.881801 · Cited by 115 · see citing works
Zheng, 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 · see citing works
Isolation and 3D expansion of multipotent Sox9+ mouse lung progenitors
Nichane, M., Javed, A., Vijayakumar, S., Ganesan, M., Ang, L. T., Kraus, P., Lufkin, T., Loh, K. M., & Lim, B. (2017) · Nature Methods · doi:10.1038/nmeth.4498 · Cited by 93 · see citing works
Cellular Senescence: The Trojan Horse in Chronic Lung Diseases
Hamsanathan, S., Alder, J. K., Sellarés, J., Rojas, M. M., Gurkar, A. U., & Mora, A. L. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2018-0410tr · Cited by 87 · see citing works
Weiner, A. I., Jackson, S. R., Zhao, G., Quansah, K. K., Farshchian, J. N., Neupauer, K. M., Littauer, E. Q., Paris, A. J., Liberti, D. C., Worthen, G. S., et al. (2019) · npj Regenerative Medicine · doi:10.1038/s41536-019-0080-9 · Cited by 81 · see citing works
Buchweitz, J. P., Harkema, J. R., & Kaminski, N. E. (2007) · Toxicologic Pathology · doi:10.1080/01926230701302558 · Cited by 76 · see citing works
p53 Regulates Progenitor Cell Quiescence and Differentiation in the Airway
McConnell, A. M., Yao, C., Yeckes, A. R., Wang, Y., Selvaggio, A. S., Tang, J., Kirsch, D. G., & Stripp, B. R. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.11.007 · Cited by 74 · see citing works
Cellular Senescence and Lung Function during Aging. Yin and Yang
Campisi, J. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201609-703aw · Cited by 74 · see citing works
β-Catenin maintains lung epithelial progenitors after lung specification
Ostrin, E. J., Little, D. R., Gerner-Mauro, K. N., Sumner, E. A., Ríos-Corzo, R., Ambrosio, E. M., Holt, S. E., Forcioli-Conti, N., Akiyama, H., Hanash, S., et al. (2018) · Development · doi:10.1242/dev.160788 · Cited by 55 · see citing works
Differentiation of Club Cells to Alveolar Epithelial Cells In Vitro
Zheng, D., Soh, B.-S., Yin, L., Hu, G., Chen, Q., Choi, H., Han, J., Chow, V. T. K., & Chen, J. (2017) · Scientific Reports · doi:10.1038/srep41661 · Cited by 52 · see citing works
Strunz, M., Simon, L. M., Ansari, M., Mattner, L. F., Angelidis, I., Mayr, C. H., Kathiriya, J. J., Yee, M., Ogar, P., Sengupta, A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/705244 · Cited by 30 · see citing works
Self-citationEndogenous lung stem cells for lung regeneration
McQualter, J. L. (2019) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1596256 · Cited by 20 · see citing works
Origin and regulation of a lung repair kit
Chen, J. (2017) · Nature Cell Biology · doi:10.1038/ncb3585 · Cited by 14 · see citing works
Flagged first, then by citations
1 of the 46 references couldn’t be matched to a known paper.
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 710 · see citing works
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 · see citing works
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 · see citing works
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 406 · see citing works
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 263 · see citing works
Self-citationD’Agnillo, F., Walters, K.-A., Xiao, Y., Sheng, Z.-M., Scherler, K., Park, J., Gygli, S., Rosas, L. A., Sadtler, K., Kalish, H., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abj7790 · Cited by 237 · see citing works
Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models
Urzì, O., Gasparro, R., Costanzo, E., Luca, A. D., Giavaresi, G., Fontana, S., & Alessandro, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512046 · Cited by 213 · see citing works
Lung Adenocarcinoma Tumor Origin: A Guide for Personalized Medicine
Seguin, L., Durandy, M., & Féral, C. C. (2022) · Cancers · doi:10.3390/cancers14071759 · Cited by 174 · see citing works
Regulation of epithelial transitional states in murine and human pulmonary fibrosis
Wang, F., Ting, C., Riemondy, K. A., Douglas, M., Foster, K., Patel, N., Kaku, N., Linsalata, A. E., Nemzek, J. A., Varisco, B. M., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci165612 · Cited by 165 · see citing works
A census of the lung: CellCards from LungMAP
Sun, X., Perl, A. T., Li, R., Bell, S. M., Sajti, E., Kalinichenko, V. V., Kalin, T. V., Misra, R. S., Deshmukh, H. S., Clair, G., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.11.007 · Cited by 157 · see citing works
Wnt signaling in lung development, regeneration, and disease progression
Aros, C. J., Pantoja, C. J., & Gomperts, B. N. (2021) · Communications Biology · doi:10.1038/s42003-021-02118-w · Cited by 166 · see citing works
Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration
Aspal, M., & Zemans, R. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093188 · Cited by 141 · see citing works
Tracing the origin of alveolar stem cells in lung repair and regeneration
Liu, K., Meng, X., Liu, Z., Tang, M., Lv, Z., Huang, X., Jin, H., Han, X., Liu, X., Pu, W., et al. (2024) · Cell · doi:10.1016/j.cell.2024.03.010 · Cited by 138 · see citing works
Shenoy, A. T., Ana, C. L. D., Arafa, E. I., Salwig, I., Barker, K. A., Korkmaz, F. T., Ramanujan, A., Etesami, N. S., Soucy, A. M., Martin, I. M. C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26045-w · Cited by 133 · see citing works
Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration
Alysandratos, K., Herriges, M. J., & Kotton, D. N. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-041520-092904 · Cited by 114 · see citing works
Cellular senescence as a potential mediator of COVID‐19 severity in the elderly
Nehme, J., Borghesan, M., Mackedenski, S., Bird, T. G., & Demaria, M. (2020) · Aging Cell · doi:10.1111/acel.13237 · Cited by 94 · see citing works
Costa, M., Weiner, A. I., & Vaughan, A. E. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.09.006 · Cited by 90 · see citing works
Senescence of alveolar epithelial progenitor cells: a critical driver of lung fibrosis
Parimon, T., Chen, P., Stripp, B. R., Liang, J., Jiang, D., Noble, P. W., Parks, W. C., & Yao, C. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00239.2023 · Cited by 89 · see citing works
Targeted alveolar regeneration with Frizzled-specific agonists
Nabhan, A. N., Webster, J. D., Adams, J., Blazer, L. L., Everrett, C., Eidenschenk, C., Arlantico, A., Fleming, I., Brightbill, H. D., Wolters, P. J., et al. (2023) · Cell · doi:10.1016/j.cell.2023.05.022 · Cited by 83 · see citing works
Repair and regeneration of the alveolar epithelium in lung injury
Wang, Y., Wang, L., Ma, S., Cheng, L. C., & Yu, G. (2024) · The FASEB Journal · doi:10.1096/fj.202400088r · Cited by 81 · see citing works
Choi, J., Jang, Y. J., Dabrowska, C., Iich, E., Evans, K. V., Hall, H., Janes, S. M., Simons, B. D., Koo, B., Kim, J., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00742-6 · Cited by 75 · see citing works
Epithelial Cells and Inflammation in Pulmonary Wound Repair
Lucchini, A. C., Gachanja, N. N., Rossi, A., Dorward, D., & Lucas, C. D. (2021) · Cells · doi:10.3390/cells10020339 · Cited by 70 · see citing works
Physiological and immunological barriers in the lung
Kageyama, T., Ito, T. K., Tanaka, S., & Nakajima, H. (2024) · Seminars in Immunopathology · doi:10.1007/s00281-024-01003-y · Cited by 74 · see citing works
Human Lung Organoids—A Novel Experimental and Precision Medicine Approach
Kühl, L., Graichen, P., von Daacke, N., Mende, A., Wygrecka, M., Potaczek, D. P., Miethe, S., & Garn, H. (2023) · Cells · doi:10.3390/cells12162067 · Cited by 66 · see citing works
WNT Signaling in Lung Repair and Regeneration.
Raslan, A., & Yoon, J. K. (2020) · PubMed Central · doi:10.14348/molcells.2020.0059 · Cited by 63 · see citing works
Huang, Q., Wang, Y., Zhang, L., Qian, W., Shen, S., Wang, J., Wu, S., Xu, W. Q., Chen, B., Lin, M., et al. (2022) · Respiratory Research · doi:10.1186/s12931-022-02293-2 · Cited by 64 · see citing works
Ma, L., Thapa, B. R., Suer, J. A. L., Tilston-Lünel, A., Herriges, M. J., Berical, A. C., Beermann, M. L., Wang, F., Bawa, P., Kohn, A., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.07.014 · Cited by 63 · see citing works
Host Recovery from Respiratory Viral Infection
Wei, X., Narasimhan, H., Zhu, B., & Sun, J. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-040450 · Cited by 61 · see citing works
Targeting Alveolar Repair in Idiopathic Pulmonary Fibrosis
Ptasinski, V., Stegmayr, J., Belvisi, M. G., Wagner, D. E., & Murray, L. A. (2021) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0476tr · Cited by 59 · see citing works
Telomeres and Telomerase in the Control of Stem Cells
Lupatov, A. Y., & Yarygin, K. N. (2022) · Biomedicines · doi:10.3390/biomedicines10102335 · Cited by 61 · see citing works
SARS-CoV-2 Infection and Lung Regeneration
Zhao, F., Ma, Q., Yue, Q., & Chen, H. (2022) · Clinical Microbiology Reviews · doi:10.1128/cmr.00188-21 · Cited by 57 · see citing works
Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice
Herriges, M. J., Yampolskaya, M., Thapa, B. R., Lindstrom-Vautrin, J., Wang, F., Huang, J., Na, C.-L., Ma, L., Montminy, M. M., Bawa, P., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.07.016 · Cited by 57 · see citing works
Progenitor potential of lung epithelial organoid cells in a transplantation model
Louie, S. M., Moye, A. L., Wong, I. G., Lu, E., Shehaj, A., de Alba, C. G., Ararat, E., Raby, B. A., Lu, B., Paschini, M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110662 · Cited by 52 · see citing works
Organoid: a powerful tool to study lung regeneration and disease
Lu, T., Cao, Y., Zhao, P., Shen, S., & Xi, Y. (2021) · Cell Regeneration · doi:10.1186/s13619-021-00082-8 · Cited by 52 · see citing works
Sidarta-Oliveira, D., Jara, C. P., Ferruzzi, A. J., Skaf, M. S., Velander, W. H., ARAUJO, E. P. D., & Velloso, L. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-76488-2 · Cited by 53 · see citing works
An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease
Blackburn, J. B., Li, N. F., Bartlett, N. W., & Richmond, B. W. (2023) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00192.2022 · Cited by 51 · see citing works
Beppu, A., Zhao, J., Yao, C., Carraro, G., Israely, E., Coelho, A. L., Drake, K., Hogaboam, C. M., Parks, W. C., Kolls, J. K., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41387-3 · Cited by 46 · see citing works
Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation
Crotta, S., Villa, M., Major, J., Finsterbusch, K., Llorian, M., Carmeliet, P., Buescher, J. M., & Wack, A. (2023) · Nature Communications · doi:10.1038/s41467-023-36352-z · Cited by 48 · see citing works
Interleukin-6–dependent epithelial fluidization initiates fibrotic lung remodeling
Stancil, I. T., Michalski, J. E., Hennessy, C. E., Hatakka, K. L., Yang, I. V., Kurche, J. S., Rincón, M., & Schwartz, D. A. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abo5254 · Cited by 48 · see citing works
Organoid models: assessing lung cell fate decisions and disease responses
Liberti, D. C., & Morrisey, E. E. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.09.008 · Cited by 45 · see citing works
Weiner, A. I., Zhao, G., Zayas, H. M., Holcomb, N. P., Adams‐Tzivelekidis, S., Wong, J., Gentile, M. E., Reddy, D., Wei, J., Palashikar, G., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111805 · Cited by 47 · see citing works
The critical role of osteopontin (OPN) in fibrotic diseases
Tang, Z., Xia, Z., Wang, X., & Liu, Y. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.08.007 · Cited by 47 · see citing works
Alveolar regeneration by airway secretory-cell-derived p63+ progenitors
Lv, Z., Liu, Z., Liu, K., Lin, X., Pu, W., Li, Y., Zhao, H., Xi, Y., Sui, P., Vaughan, A. E., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.08.005 · Cited by 46 · see citing works
Stem cells in pulmonary alveolar regeneration
Wu, H., & Tang, N. (2021) · Development · doi:10.1242/dev.193458 · Cited by 43 · see citing works
Heterogeneous groups of alveolar type II cells in lung homeostasis and repair
Chen, Q., & Liu, Y. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00341.2020 · Cited by 46 · see citing works
Complex Analysis of Single-Cell RNA Sequencing Data
Khozyainova, A. A., Valyaeva, A. A., Arbatsky, M. S., Isaev, S. V., Iamshchikov, P. S., Volchkov, E., Sabirov, M. S., Zainullina, V. R., Chechekhin, V. I., Vorobev, R. S., et al. (2023) · Biochemistry (Moscow) · doi:10.1134/s0006297923020074 · Cited by 46 · see citing works
Valyaeva, A. A., Zharikova, A. A., Kasianov, A. S., Vassetzky, Y. S., & Sheval, E. V. (2020) · Scientific Reports · doi:10.1038/s41598-020-74598-5 · Cited by 44 · see citing works
Hermelijn, S. M., Wolf, J. L., den Toom, T. D., Wijnen, R. M. H., Rottier, R. J., Schnater, J. M., & von der Thüsen, J. H. (2020) · Human Pathology · doi:10.1016/j.humpath.2020.07.015 · Cited by 43 · see citing works
A transitional stem cell state in the lung
Verheyden, J. M., & Sun, X. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0561-5 · Cited by 43 · see citing works
Ting, C., Aspal, M., Vaishampayan, N., Huang, S. K., Riemondy, K. A., Wang, F., Farver, C. F., & Zemans, R. L. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.11.014 · Cited by 42 · see citing works
Function of epithelial stem cell in the repair of alveolar injury
Chan, M., & Liu, Y. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02847-7 · Cited by 41 · see citing works
VEGF receptor 2 (KDR) protects airways from mucus metaplasia through a Sox9-dependent pathway
Jiang, M. Z., Fang, Y., Li, Y., Huang, H., Wei, Z., Gao, X., Sung, H., Hu, J., Qiang, L., Ruan, J., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.027 · Cited by 40 · see citing works
Hu, Y., Hu, Q., Ansari, M., Riemondy, K. A., Pineda, R., Sembrat, J., Leme, A. S., Ngo, K., Morgenthaler, O., Ha, K., et al. (2024) · European Respiratory Journal · doi:10.1183/13993003.02071-2023 · Cited by 39 · see citing works
Current advancements in nanotechnology for stem cells
Thamarai, P., Karishma, S., Kamalesh, R., Shaji, A., Saravanan, A., Bibi, S., Vickram, A. S., Chopra, H., Saleem, R. A., Alsharif, K. F., et al. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000002082 · Cited by 37 · see citing works
Sun, Y. L., Hurley, K., Villacorta-Martín, C., Huang, J., Hinds, A., Gopalan, K., Caballero, I. S., Russo, S. J., Kitzmiller, J. A., Whitsett, J. A., et al. (2021) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0259oc · Cited by 37 · see citing works
Wang, Y., Meng, Z., Liu, M., Zhou, Y., Chen, D., Zhao, Y., Zhang, T., Zhong, N., Dai, X., Li, S., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi3360 · Cited by 37 · see citing works
Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis
Kumar, A., Elko, E. A., Bruno, S. R., Mark, Z. F., Chamberlain, N., Korwin-Mihavics, B. R., Chandrasekaran, R., Walzer, J., Ruban, M., Gold, C., et al. (2021) · Thorax · doi:10.1136/thoraxjnl-2021-216882 · Cited by 40 · see citing works
Hong, X., Wang, L., Zhang, K., Liu, J., & Liu, J. (2022) · Cells · doi:10.3390/cells11050877 · Cited by 35 · see citing works
Heydemann, L., Ciurkiewicz, M., Beythien, G., Becker, K., Schughart, K., Stanelle‐Bertram, S., Schaumburg, B., Kouassi, N. M., Beck, S., Zickler, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39049-5 · Cited by 35 · see citing works
Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium
Bridges, J. P., Vladar, E. K., Kurche, J. S., Krivoi, A., Stancil, I. T., Dobrinskikh, E., Hu, Y., Sasse, S. K., Lee, J. S., Blumhagen, R. Z., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci183836 · Cited by 37 · see citing works
Huang, K. Y., & Petretto, E. G. (2021) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00594.2020 · Cited by 35 · see citing works
Impaired Alveolar Re-Epithelialization in Pulmonary Emphysema
Lin, C.-R., Bahmed, K., & Kośmider, B. (2022) · Cells · doi:10.3390/cells11132055 · Cited by 34 · see citing works
Club cells employ regeneration mechanisms during lung tumorigenesis
Chen, Y., Tóth, R., Chocarro, S., Weichenhan, D., Hey, J., Lutsik, P., Sawall, S., Stathopoulos, G. T., Plass, C., & Sotillo, R. (2022) · Nature Communications · doi:10.1038/s41467-022-32052-2 · Cited by 36 · see citing works
New Insights into the Alveolar Epithelium as a Driver of Acute Respiratory Distress Syndrome
Zuttion, M. S. S. R., Moore, S. K., Chen, P., Beppu, A., & Hook, J. L. (2022) · Biomolecules · doi:10.3390/biom12091273 · Cited by 34 · see citing works
Epithelial stem cells and niches in lung alveolar regeneration and diseases
Zhang, J., & Liu, Y. (2024) · Chinese Medical Journal - Pulmonary and Critical Care Medicine · doi:10.1016/j.pccm.2023.10.007 · Cited by 35 · see citing works
Lung regeneration: diverse cell types and the therapeutic potential
Chen, Y., Li, Z., Ji, G., Wang, S., Mo, C., & Ding, B. (2024) · MedComm · doi:10.1002/mco2.494 · Cited by 35 · see citing works
IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis
Auyeung, V. C., Downey, M. S., Kathiriya, J. J., Thamsen, M., Wenger, T. A., Backes, B. J., Brumwell, A. N., Chapman, H. A., Sheppard, D., & Papa, F. R. (2022) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00408.2021 · Cited by 34 · see citing works
Self-citationMcCall, A. S., Gutor, S. S., Tanjore, H., Burman, A., Sherrill, T. P., Chapman, M., Calvi, C. L., Han, D., Camarata, J. E., Hunt, R. P., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adk8623 · Cited by 31 · see citing works
You Say You Want a Resolution (of Fibrosis)
Atabai, K., Yang, C. D., & Podolsky, M. J. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0182tr · Cited by 30 · see citing works
Abnormal respiratory progenitors in fibrotic lung injury
Xie, T., Lynn, H., Parks, W. C., Stripp, B. R., Chen, P., Jiang, D., & Noble, P. W. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02737-y · Cited by 29 · see citing works
New Perspectives on the Aberrant Alveolar Repair of Idiopathic Pulmonary Fibrosis
Wang, Z. N., & Tang, X. X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.580026 · Cited by 30 · see citing works
Self-citationClub‐like cells in proliferative inflammatory atrophy of the prostate
Huang, F. W., Song, H., Weinstein, H. N. W., Xie, J., Cooperberg, M. R., Hicks, J. L., Mummert, L. A., Marzo, A. M. D., & Sfanos, K. S. (2023) · The Journal of Pathology · doi:10.1002/path.6149 · Cited by 30 · see citing works
Single‐cell analysis identified lung progenitor cells in COVID‐19 patients
Zhao, Z., Zhao, Y., Zhou, Y., Wang, X., Zhang, T., & Zuo, W. (2020) · Cell Proliferation · doi:10.1111/cpr.12931 · Cited by 29 · see citing works
3D bioprinting of the airways and lungs for applications in tissue engineering and in vitro models
Zhang, Y., Liu, Y., Shu, C., Shen, Y., Li, M., Ma, N., & Zhao, J. (2024) · Journal of Tissue Engineering · doi:10.1177/20417314241309183 · Cited by 28 · see citing works
Stem cell migration drives lung repair in living mice
Chioccioli, M., Liu, S., Magruder, S., Tata, A., Borriello, L., McDonough, J. E., Konkimalla, A., Kim, S., Nouws, J., Gonzalez, D. G., et al. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.02.003 · Cited by 26 · see citing works
Lung Regeneration: Cells, Models, and MechanismsPreprint
Konkimalla, A., Tata, A., & Tata, P. R. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040873 · Cited by 26 · see citing works
Rowbotham, S. P., Pessina, P., de Alba, C. G., Jensen, J., Nguyen, Y., Yoon, J. H., Li, J., Wong, I. G., Fahey, C., Moye, A. L., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.10.011 · Cited by 25 · see citing works
Wang, J., Peng, X., Yuan, N., Wang, B., Chen, S., Wang, B., & Xie, L. (2024) · Translational research · doi:10.1016/j.trsl.2024.05.012 · Cited by 26 · see citing works
Hong, X., Nie, H., Deng, J., Liang, S., Chen, L., Li, J., Gong, S., Wang, G., Zuo, W., Hou, F. F., et al. (2023) · Theranostics · doi:10.7150/thno.79326 · Cited by 25 · see citing works
Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid culturesPreprint
Salahudeen, A. A., Choi, S. S., Rustagi, A., Zhu, J., Sean de la, O., Flynn, R. A., Margalef-Català, M., Santos, A. J. M., Ju, J., Batish, A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.27.212076 · Cited by 25 · see citing works
Lin, X., Chen, W., Yang, G., Zhang, J., Wang, H., Liu, Z., Xi, Y., Ren, T., Liu, B., & Sui, P. (2024) · Journal of Clinical Investigation · doi:10.1172/jci176828 · Cited by 23 · see citing works
Regulation of lung progenitor plasticity and repair by fatty acid oxidation
Angeles-López, Q. D., Rodriguez-Lopez, J., Garcia, P. A., Calyeca, J., Álvarez, D., Bueno, M., Tu, L. N., Salazar-Terreros, M. J., Vanegas-Avendaño, N., Krull, J. E., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.165837 · Cited by 23 · see citing works
PCLAF-DREAM drives alveolar cell plasticity for lung regeneration
Kim, B.-J., Huang, Y., Ko, K.-P., Zhang, S., Zou, G., Zhang, J., Kim, M. J., Little, D. T., Ellis, L. V., Paschini, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53330-1 · Cited by 23 · see citing works
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
Furnon, W., Cowton, V. M., Lorenzo, G. D., Orton, R. J., Herder, V., Cantoni, D. M., Ilia, G., Mendonça, D. C., Kerr, K., Allan, J., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-024-01878-5 · Cited by 23 · see citing works
Lipolysis engages CD36 to promote ZBP1-mediated necroptosis-impairing lung regeneration in COPD
Wang, J., Wang, R., Li, Y., Huang, J.-H., Liu, Y., Wang, J., Xian, P., Zhang, Y., Yang, Y., Zhang, H., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101732 · Cited by 21 · see citing works
Khan, P., Roux, J., Blumer, S., Fang, L., Savic, S., Knudsen, L., Jonigk, D., Kuehnel, M. P., Gazdhar, A., Geiser, T., et al. (2022) · Cells · doi:10.3390/cells11111820 · Cited by 20 · see citing works
Intermediary Role of Lung Alveolar Type 1 Cells in Epithelial Repair upon Sendai Virus Infection
Hernandez, B. J., Cain, M. P., Lynch, A. M., Flores, J. R., Tuvim, M. J., Dickey, B. F., & Chen, J. (2022) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2021-0421oc · Cited by 20 · see citing works
Regeneration-Associated Transitional State Cells in Pulmonary Fibrosis
Shen, M., Luo, Z., & Zhou, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126757 · Cited by 20 · see citing works
Egea-Zorrilla, A., Vera, L., Sáez, B., & Pardo–Saganta, A. (2022) · Cells · doi:10.3390/cells11162595 · Cited by 20 · see citing works
Martins, L. R., Sieverling, L., Michelhans, M., Schiller, C., Erkut, C., Grünewald, T. G. P., Triana, S., Fröhling, S., Velten, L., Glimm, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46469-4 · Cited by 20 · see citing works
Shen, S., Wang, P., Wu, P.-H., Huang, P., Chi, T. H., Xu, W., & Xi, Y. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.09.008 · Cited by 19 · see citing works
Kim, J., Eo, E., Kim, B., Lee, H., Kim, J., Koo, B., Kim, H., Cho, S., Kim, J.-H., & Cho, Y. (2024) · Cells · doi:10.3390/cells13231991 · Cited by 20 · see citing works
Cloned airway basal progenitor cells to repair fibrotic lung through re-epithelialization
Zhao, Y., Zhou, Y., Zhang, W., Liu, M., Duan, J., Zhang, X., Ma, Q., Wang, Y., Zhang, Y., Guo, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56501-w · Cited by 19 · see citing works
IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells
Cai, X. T., Jia, M., Heigl, T., Shamir, E. R., Wong, A. K., Hall, B. M., Arlantico, A., Hung, J., Menon, H. G., Darmanis, S., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114569 · Cited by 19 · see citing works
Lung and Eye Disease Develop Concurrently in Supplemental Oxygen–Exposed Neonatal Mice
Wickramasinghe, L. C., Lau, M., Deliyanti, D., Gottschalk, T. A., van Wijngaarden, P., Talia, D. M., Johnson, C. J., Wilkinson‐Berka, J. L., Tsantikos, E., & Hibbs, M. L. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.05.016 · Cited by 19 · see citing works
Xu, L., Tan, C., Barr, J., Talaba, N., Verheyden, J. M., Chin, J., Gaboyan, S., Kasaraneni, N., Elgamal, R. M., Gaulton, K. J., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.08.001 · Cited by 20 · see citing works
Immunological and regenerative properties of lung stem cells
Hao, D., Liu, Y., Li, L., Stripp, B. R., & Chen, H. (2025) · Physiological Reviews · doi:10.1152/physrev.00056.2024 · Cited by 19 · see citing works
Circadian regulation of lung repair and regeneration
Naik, A., Forrest, K., Paul, O., Issah, Y., Valekunja, U., Tang, S., Reddy, A. B., Hennessy, E., Brooks, T. G., Chaudhry, F. N., et al. (2021) · bioRxiv · doi:10.1172/jci.insight.164720 · Cited by 25 · see citing works
Pezet, M. G., Torres, J. A., Thimraj, T. A., Matković, I., Schrode, N., Murray, J. W., Saqi, A., Beaumont, K. G., & Snoeck, H. (2025) · Nature Biotechnology · doi:10.1038/s41587-025-02569-0 · Cited by 16 · see citing works
BCL-2 Modulates IRE1α Activation to Attenuate Endoplasmic Reticulum Stress and Pulmonary Fibrosis
Saux, C. J. L., Ho, T. C., Brumwell, A. M., Kathiriya, J. J., Wei, Y. J., Hughes, J. B., Garakani, K., Atabai, K., Auyeung, V. C., Papa, F. R., et al. (2023) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2023-0109oc · Cited by 16 · see citing works
Self-citation
- 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
