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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.
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“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
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“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
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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
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
Items 701–800 of 1,000
Ikeo, S., Yamamoto, Y., Ikeda, K., Sone, N., Korogi, Y., Tomiyama, L., Matsumoto, H., Hirai, T., Hagiwara, M., & Gotoh, S. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121031 · Cited by 25
“Considering that AT2 cells play important roles as tissue stem cells [8], we expect that this humanized lung mouse model will be a useful tool for research on lung regeneration.”
BackgroundCo-culture of type I and type II pneumocytes as a model of alveolar epithelium
Brookes, O., Boland, S., Lai–Kuen, R., Miremont, D., Movassat, J., & Baeza‐Squiban, A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248798 · Cited by 25
“There is an ontogenic relationship between the two, in that Type II epithelial cells terminally differentiate into Type I cells [15], although recent research indicates that both type I and type II cells comprise of multiple subtypes with differing degrees of developmental plasticity [16–19], with their own niches and…”
BackgroundA role for club cells in smoking-associated lung adenocarcinoma
Behrend, S. J., Giotopoulou, G. A., Σπέλλα, Μ., & Stathopoulos, G. T. (2021) · European Respiratory Review · doi:10.1183/16000617.0122-2021 · Cited by 24
Ali, M., Zhang, X., LaCanna, R., Tomar, D., Elrod, J. W., & Tian, Y. (2022) · JCI Insight · doi:10.1172/jci.insight.154447 · Cited by 23
“These AT2 cell activities are vital to alveolar epithelial repair and regeneration (1, 2).”
BackgroundMethodThree-dimensional models of the lung: past, present and future: a mini review
Sen, C., Freund, D., & Gomperts, B. N. (2022) · Biochemical Society Transactions · doi:10.1042/bst20190569 · Cited by 25
Lung Organoids in Smoking Research: Current Advances and Future Promises
Agraval, H., & Chu, H. W. (2022) · Biomolecules · doi:10.3390/biom12101463 · Cited by 25
“It was noted that mesenchymal cells as a feeder layer promote the self-renewal of AEC2 cells [65].”
BackgroundMethodInfluentialChen, J., & Na, F. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1066869 · Cited by 25
Chignalia, A. Z., Vogel, S. M., Reynolds, A. B., Mehta, D., Dull, R. O., Minshall, R. D., Malik, A. B., & Liu, Y. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.01.022 · Cited by 25
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
Comprehensive Review of the Vascular Niche in Regulating Organ Regeneration and Fibrosis
Chen, Y., & Ding, B. (2022) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szac070 · Cited by 26
Chen, X., Zhang, C., Wei, T., Chen, J., Pan, T. S., Li, M., Wang, L., Song, J., Chen, C., Zhang, Y., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.162547 · Cited by 24
“However, little is known about the physiological function of 239 α7nAChR in alveolar regeneration, which relies on the proliferation and proliferation of AT2 cells 240 (23, 24).”
BackgroundInterleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration
Ng, B., Huang, K. Y., Pua, C. J., Viswanathan, S., Lim, W., Kuthubudeen, F. F., Liu, Y., Hii, A. A., George, B. L., Widjaja, A. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52810-8 · Cited by 24
“AT2 cell proliferation is crucial for alveolar repair after injury (1, 31, 32) and we tested the effects of IL11 or TGFβ1 on AT2 cell proliferation.”
BackgroundMethodReinecke, J. B., Garcia, L. J., Gross, A. C., Cam, M., Cannon, M. V., Gust, M. J., Sheridan, J. P., Gryder, B. E., Dries, R., & Roberts, R. D. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-0049 · Cited by 25
“This finding was consistent with the physiologic reaction to alveolar injury, as AEC2 cells are facultative stem cells within the alveolus, functioning to reestablish epithelial barrier integrity after AEC1 injury (27).”
Kondo, H., Miyoshi, K., Sakiyama, S., Tangoku, A., & Noma, T. (2015) · Stem Cells International · doi:10.1155/2015/165867 · Cited by 24
Reserve Autophagic Capacity in Alveolar Epithelia Provides a Replicative Niche for Influenza A Virus
Hahn, D., Na, C.-L., & Weaver, T. E. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0437oc · Cited by 24
Leibel, S. L., & Post, M. (2016) · Frontiers in Pediatrics · doi:10.3389/fped.2016.00036 · Cited by 24
“Finally, ATII cells in the alveoli give rise to ATI cells although the rate of conversion depends on whether the cells are in steady state (slow rate) or during repair after injury (fast rate) (18, 26).”
BackgroundBohaud, C., Johansen, M. D., Jørgensen, C., Kremer, L., Ipseiz, N., & Djouad, F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.707856 · Cited by 25
“The final structure of the bronchial tree, the alveoli, comprises two types of epithelial cells: type I alveolar (AT1) and type II alveolar (AT2) cells (96).”
BackgroundThe role of miRNAs in alveolar epithelial cells in emphysema
Hayek, H., Kośmider, B., & Bahmed, K. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112216 · Cited by 26
Organ Specificity and Heterogeneity of Cancer-Associated Fibroblasts in Colorectal Cancer
Miyashita, N., & Saito, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010973 · Cited by 27
“For instance, clonal growth and differentiation of alveolar epithelial cells can be achieved when co-cultured with lung fibroblasts [7].”
BackgroundAirway secretory cell fate conversion via YAP‐mTORC1‐dependent essential amino acid metabolism
Jeon, H. Y., Choi, J., Kraaier, L. J., Kim, Y. H., Eisenbarth, D., Yi, K., Kang, J., Kim, J. W., Shim, H. S., Lee, J., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021109365 · Cited by 23
Lung Cancer Organoids: The Rough Path to Personalized Medicine
Rossi, R., Angelis, M. L. D., Xhelili, E., Sette, G., Eramo, A., Maria, R. D., Incani, U. C., Francescangeli, F., & Zeuner, A. (2022) · Cancers · doi:10.3390/cancers14153703 · Cited by 27
Senescent AECⅡ and the implication for idiopathic pulmonary fibrosis treatment
Zhang, T., Zhang, J., Lv, C., Li, H., & Song, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1059434 · Cited by 25
“When lung tissues are damaged, AECIIs can differentiate into AECIs, which are involved in epithelial repair (Barkauskas et al., 2013).”
BackgroundLong, Y., Wang, G., Li, K., Zhang, Z., Zhang, P., Zhang, J., Zhang, X., Bao, Y., Yang, X., & Wang, P. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1496743 · Cited by 24
“AECII cells can self-replicate and serve as adult stem cells to differentiate into AECI cells during normal homeostatic turnover, or when AECI cells become depleted due to injury [9,10].”
BackgroundTanaka, Y., Yamaguchi, M., Hirai, S., Sumi, T., Tada, M., Saito, A., Chiba, H., Kojima, T., Watanabe, A., Takahashi, H., et al. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.09.020 · Cited by 24
A method of generating alveolar organoids using human pluripotent stem cells
Yamamoto, Y., Korogi, Y., Hirai, T., & Gotoh, S. (2020) · Methods in cell biology · doi:10.1016/bs.mcb.2020.02.004 · Cited by 24
Developmental programs of lung epithelial progenitors: a balanced progenitor model
Yang, J., & Chen, J. (2014) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.141 · Cited by 24
SIRT1: An Intermediator of Key Pathways Regulating Pulmonary Diseases
Jiang, Y.-Z., Huang, X.-R., Chang, J., Zhou, Y., & Huang, X.-T. (2024) · Laboratory Investigation · doi:10.1016/j.labinv.2024.102044 · Cited by 24
Moghaddam, S. J., Savai, R., Salehi‐Rad, R., Sengupta, S., Kammer, M. N., Massion, P. P., Beane, J., Ostrin, E. J., Priolo, C., Tennis, M. A., et al. (2024) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202406-1168st · Cited by 26
“Among the best characterized progenitor cells are alveolar type II epithelial (AT2) cells (52, 53).”
BackgroundLin, 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 25
Lipoxin A 4 promotes lung epithelial repair whilst inhibiting fibroblast proliferation
Zheng, S., D’Souza, V., Bartis, D., Dancer, R. C. A., Parekh, D., Naidu, B. V., Smith, F. G., Wang, Q., Jin, S., Lian, Q., et al. (2016) · ERJ Open Research · doi:10.1183/23120541.00079-2015 · Cited by 23
It takes a village: Phagocytes play a central role in fungal immunity
Feldman, M. B., Vyas, J. M., & Mansour, M. K. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.04.008 · Cited by 27
TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis
Cong, X., Nagre, N. N., Herrera, J., Pearson, A. C., Pepper, I., Morehouse, R., Ji, H., Jiang, D., Hubmayr, R. D., & Zhao, X. (2020) · Respiratory Research · doi:10.1186/s12931-020-01384-2 · Cited by 23
Costa, R., Wagner, D. E., Doryab, A., Santis, M. M. D., Schorpp, K., Rothenaigner, I., Lehmann, M., Baarsma, H. A., Liu, X., Schmid, O., et al. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15581 · Cited by 25
“Organoids were cultured as previously described (Barkauskas et al., 2013; Hu et al., 2020; Ng-Blichfeldt et al., 2018, Lehmann et al., 2020) with some modifications.”
MethodAhmadvand, N., Lingampally, A., Khosravi, F., Vazquez‐Armendariz, A. I., Rivetti, S., Jones, M. R., Wilhelm, J., Herold, S., Barreto, G., Koepke, J., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04327-w · Cited by 21
Tsukui, T., Ueha, S., Shichino, S., Inagaki, Y., & Matsushima, K. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.07.022 · Cited by 28
“17,18 An endothelial basement membrane separated Col-GFP þ cells from the majority of the endothelium, a characteristic that distinguished these cells from PDGFR b þ pericytes, which were convoluted within the endothelial basement membrane (Figure 1, F and G).”
BackgroundPagano, F., Nocella, C., Sciarretta, S., Fianchini, L., Siciliano, C., Mangino, G., Ibrahim, M., FALCO, E. D., Carnevale, R., Chimenti, I., et al. (2017) · American Journal of Transplantation · doi:10.1111/ajt.14278 · Cited by 23
“Intriguingly, our results suggest that Steen solution may maintain the integrity of donor lungs in EVLP also by preserving, at least in part, a regenerative cellular pool actively involved in injury resolution through resident LPCs and epithelial cells, which can behave like lung stem cells themselves (7,8,20,30).”
BackgroundJarvis, I. W. H., Enlo‐Scott, Z., Nagy, E., Mudway, I., Tetley, T. D., Arlt, V. M., & Phillips, D. H. (2018) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22166 · Cited by 23
“Type II cells are capable of cell division and act as the main progenitor cells during repair of alveolar damage, functioning as self-renewing cells, and precur- sors of Type I cells [Barkauskas et al., 2013].”
BackgroundHung, L., Oniskey, T. K., Sen, D., Krummel, M. F., Vaughan, A. E., Cohen, N. A., & Herbert, D. R. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.01.020 · Cited by 23
Culture of human alveolar epithelial type II cells by sprouting
Khan, P., Fytianos, K., Tamò, L., Roth, M., Tamm, M., Geiser, T., Gazdhar, A., & Hostettler, K. (2018) · Respiratory Research · doi:10.1186/s12931-018-0906-9 · Cited by 23
Chen, X., Zhao, C., Zhang, C., Li, Q., Chen, J., Cheng, L., Zhou, J., Su, X., & Song, Y. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01757-w · Cited by 23
“In addition, it has been reported that FGF10 is also expressed on a population of lipofibroblasts that are spatially associated with AEC2 cells [39].”
Regenerative Medicine of Epithelia: Lessons From the Past and Future Goals
Maurizi, E., Adamo, D., Magrelli, F. M., Galaverni, G., Attico, E., Merra, A., Maffezzoni, M. B. R., Losi, L., Genna, V. G., Sceberras, V., et al. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.652214 · Cited by 24
Three-Dimensional Imaging in Stem Cell-Based Researches
Nowzari, F., Wang, H., Khoradmehr, A., Baghban, M., Baghban, N., Arandian, A., Muhaddesi, M., Nabipour, I., Zibaii, M. I., Najarasl, M., et al. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.657525 · Cited by 23
“one-/two-photon confocal Fluorescence labeling (50, 51)”
Genetic architecture of human fibrotic diseases: disease risk and disease progression
Gardet, A., Zheng, T. S., & Viney, J. L. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00159 · Cited by 23
“, Xu, C., Lu, Y., Xie, G., Lu, Y., et al. (2009). Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.”
BackgroundInfluentialPCLAF-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 25
“AT2 cells replenish AT1 cells during lung regeneration 30 .”
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
“…epithelial hyperplasia is due to proliferation of type-2 pneumocytes (or other lung progenitor cells) in response to damage or loss of type-1 pneumocytes, while increased levels of macrophages and T cells in the lungs are in response to virus-induced inflammation/ immune-activation 72,78–80 .”
The best laid schemes of airway repair
Rawlins, E. L., & Giangreco, A. (2014) · European Respiratory Journal · doi:10.1183/09031936.00088014 · Cited by 22
Cell Therapy in Idiopathic Pulmonary Fibrosis†
Serrano‐Mollar, A. (2018) · Medical Sciences · doi:10.3390/medsci6030064 · Cited by 22
“Moreover, lineage-tracing analysis has also shown that ATII cells not only generate ATI cells, but can also self-renew, thus qualifying these cells as stem/progenitor cells of the adult lung alveoli [65].”
BackgroundRecent Insights into Cellular Crosstalk in Respiratory and Gastrointestinal Mucosal Immune Systems
Kim, S., & Jang, Y. (2020) · Immune Network · doi:10.4110/in.2020.20.e44 · Cited by 22
“AT2 cells act as alveolar epithelial progenitors when they detect the Wnt signal released from fibroblasts; in a steady-state condition, Wnt-responsive AT2 cells can self-renew and differentiate into AT1 cells, a process that is regulated by bone morphogenetic protein signaling (21).”
BackgroundBenzo[a]pyrene induces fibrotic changes and impairs differentiation in lung stem cells
Tseng, Y., Chen, Y., Yu, A. L.-T., & Yu, J. (2021) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2021.111892 · Cited by 22
Liu, J., Peng, D.-Y., You, J., Ou, Z., Qiu, H., Hao, C., Chen, H., Fu, Z., & Zou, L. (2021) · Stem Cells and Development · doi:10.1089/scd.2020.0208 · Cited by 23
“Sur-factant proteins are special markers of AEC2s, especially SP-C [37].”
Repairing damaged lungs using regenerative therapy
Khedoe, P. P. S. J., Wu, X., Gosens, R., & Hiemstra, P. S. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.05.002 · Cited by 22
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Allen, N. C., Reyes, N. S., Lee, J. Y., & Peng, T. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.932723 · Cited by 24
Moura, J. A., Meldrum, K., Doak, S. H., & Clift, M. J. D. (2023) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.12.006 · Cited by 26
Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology
Knudsen, L., Hummel, B., Wrede, C., Zimmermann, R., Perlman, C. E., & Smith, B. J. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1142221 · Cited by 24
“They have the potential for self-renewal and are able to transdifferentiate into AE1 cells so that AE2 cells are responsible for the regeneration of the alveolar epithelium under physiological and pathophysiological conditions (Barkauskas et al., 2013; Jansing et al., 2017).”
BackgroundCheng, H., Feng, D., Li, X., Gao, L., Qiu, Y.-J., Liang, X.-Y., Zhou, Y., Huang, P., Shao, M., Zhang, Y., et al. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2023.119535 · Cited by 22
Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury
Mao, Y., Chen, Y., Li, Y., Ma, L., Wang, X., Wang, Q. M., He, A., Liu, X., Dong, T., Gao, W., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113689 · Cited by 23
Bertho, A., Ortiz, R., Maurin, M., Juchaux, M., Gilbert, C., Espenon, J., Ramasamy, G., Patriarca, A., Marzi, L. D., Pouzoulet, F., et al. (2024) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2024.04.011 · Cited by 22
“17 They can proliferate and differentiate upon injury to repop-ulate the alveoli. pMBRT increased AT2 epithelial cells in the long term, indicating a potential proliferative response to repair the alveolus after irradiation.”
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Ren, X., & Ott, H. C. (2014) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-014-1504-4 · Cited by 22
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Möbius, M. A., & Rüdiger, M. (2016) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-016-0046-6 · Cited by 22
Zhang, L., Zhao, S., Yuan, L., Wu, H., Jiang, H., & Luo, G. (2016) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12592 · Cited by 22
Forred, B. J., Daugaard, D. R., Titus, B. K., Wood, R. R., Floen, M. J., Booze, M. L., & Vitiello, P. F. (2017) · PLoS ONE · doi:10.1371/journal.pone.0168777 · Cited by 22
Reconstructing the pulmonary niche with stem cells: a lung story
Varghese, B., Ling, Z., & Ren, X. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02830-2 · Cited by 23
“AEC2s isolated from mice were first accounted to generate alveolar organoids in 2013; FACSenriched AEC2s cultured in an ALI/Matrigel system along with primary Pdgfrα-positive lung fibroblasts were shown to form 3D spherical structures termed “alveolospheres” comprising Sftpc-positive AEC2s and cells positive for AEC1…”
BackgroundDevaux, C. A., & Camoin-Jau, L. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1042200 · Cited by 20
“Alveolar epithelial type II cells (which represent ∼5% of the alveoli and serves at stem cells to generate type I alveolar epithelial cells), are thought to be a main target for SARS-CoV-2 in the respiratory tract and, consequently, can be destroyed during viral replication (Barkauskas et al., 2013).”
BackgroundLipolysis 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
Seasock, M. J., Shafiquzzaman, M., Echartea, M. E. R., Kanchi, R. S., Tran, B. T., Simon, L. M., Meyer, M. D., Erice, P. A., Lotlikar, S. L., Wenlock, S. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59641-1 · Cited by 23
“8b, Supplementary Data 7).”
Panagiotidis, G., Vásquez‐Pacheco, E., Chu, X., Seeger, W., Agha, E. E., Bellusci, S., & Lingampally, A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1609509 · Cited by 22
Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis
Rodríguez, L. R., Alysandratos, K., Katzen, J. B., Murthy, A., Barboza, W. R., Tomer, Y., Bui, S., Perez, R. A., Petcherski, A., Minakin, K., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.182578 · Cited by 24
“Consequently, AT2 cell dysfunction has emerged as a driver of sustained fibrosis, rather than AT2 cell loss (11), which results in a resolving fibrotic response (24, 25).”
Chen, Y., Li, M., Yang, J., Chen, Y., & Wang, J. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04490-4 · Cited by 22
“However, in PF patients, ATII cells are functionally impaired, showing senescence, increased apoptosis, decreased regenerative capacity, and abnormal differentiation [34].”
Impaired non-homologous end joining in human primary alveolar type II cells in emphysema
Kośmider, B., Lin, C.-R., Vlasenko, L., Marchetti, N. T., Bolla, S., Criner, G. J., Messier, E. M., Reisdorph, N. A., Powell, R. L., Madesh, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-37000-z · Cited by 21
Wang, L., Wu, T., Hong, J., Chen, G. T. Y., Yu, J., Wang, C., & Ballini, A. (2020) · Stem Cells International · doi:10.1155/2020/6312053 · Cited by 21
“Although the progression of AECII cells and basal cells in lung tissue exposed to radiation has been studied [25, 26], the role of LSCs in RILI is still unclear.”
BackgroundKatsumiti, A., Ruenraroengsak, P., Cajaraville, M. P., Thorley, A. J., & Tetley, T. D. (2020) · Scientific Reports · doi:10.1038/s41598-020-77191-y · Cited by 23
State of the art on lung organoids in mammals
Archer, F., Erny, A., & Gomes, M. (2021) · Veterinary Research · doi:10.1186/s13567-021-00946-6 · Cited by 21
Rajabi, H., Konyalılar, N., Erkan, S., Mortazavi, D., Korkunc, S. K., Kayalar, Ö., Bayram, H., & Rahbarghazi, R. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02820-4 · Cited by 24
“Under pathological conditions like inhalation of toxic gas NO2, proliferate and differentiate into type 1 alveolar pneumocytes (AT1) [113].”
BackgroundRegenerative medicine technologies applied to transplant medicine. An update
Petrosyan, A., Montali, F., Peloso, A., Citro, A., Byers, L. N., Pointe, C. L., Suleiman, M., Marchetti, A., McNeill, E. P., Speer, A. L., et al. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1015628 · Cited by 22
“, 1982; Williams, 2003), and surfactantproducing alveolar type 2 (AT2) cells, which are alveolar stem cells with the potential of differentiation into AT1 cells (Rock et al., 2009; Barkauskas et al., 2013; Desai et al., 2014).”
BackgroundChen, H., Tao, X., Cao, H., Li, B., Sun, Q., Wang, W., Zou, Y., Mu, M., Tao, H., Zhao, Y., et al. (2023) · Food and Chemical Toxicology · doi:10.1016/j.fct.2023.113694 · Cited by 21
Ascher, K. B., Elliot, S. J., Rubio, G. A., & Glassberg, M. K. (2017) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2017.07.001 · Cited by 20
A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis
Cores, J., Dinh, P., Hensley, M. T., Adler, K. B., Lobo, L. J., & Cheng, K. (2020) · Stem Cells Translational Medicine · doi:10.1002/sctm.19-0167 · Cited by 23
Dissecting the Niche for Alveolar Type II Cells With Alveolar Organoids
Liao, D., & Li, H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00419 · Cited by 21
Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension
Nakanishi, T., Baldwin, H. S., Fineman, J. R., & Yamagishi, H. (2020) · Springer eBooks · doi:10.1007/978-981-15-1185-1 · Cited by 21
Senescence of Alveolar Stem Cells Drives Progressive Pulmonary FibrosisPreprint
Yao, C., Guan, X., Carraro, G., Parimon, T., Liu, X., Huang, G., Soukiasian, H. J., David, G., WEIGT, S. S., Belperio, J. A., et al. (2019) · SSRN Electronic Journal · doi:10.1101/820175 · Cited by 21
“Normal maintenance of the alveolar epithelium is accomplished through the proliferation of alveolar type 2 (AT2) cells, a facultative stem cell that produces and secretes pulmonary surfactant in its quiescent state (18).”
BackgroundSelf-citationLiu, X., Zhang, X., Yao, C., Liang, J., Noble, P. W., & Jiang, D. (2024) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2023-0363oc · Cited by 25
“Alveolar type II epithelial cells (AT2s) have been well accepted as progenitor cells that maintain alveolar homeostasis and repair damaged epithelium after injury (5).”
BackgroundSelf-citationRodrigues, F. S., Karoutas, A., Ruhland, S., Rabas, N., Rizou, T., Blasio, S. D., Ferreira, R. M. M., Bridgeman, V. L., Goldstone, R. J., Sopeña, M. L., et al. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.05.020 · Cited by 20
Organoids: Principle, application and perspective
Liu, K., Fang, X., Aazmi, A., Wang, Q., Gong, X., Chen, Z., Qin, M., Pu, C., Zhao, Y., Qiu, X., et al. (2024) · The Innovation Life · doi:10.59717/j.xinn-life.2024.100088 · Cited by 21
Lim, K., Rutherford, E. N., Delpiano, L., He, P., Lin, W., Sun, D., van den Boomen, D. J. H., Edgar, J. R., Bang, J. H., Predeus, A. V., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-024-00328-6 · Cited by 20
“Adult AT2 cells function as facultative progenitors of lung alveoli that can self-renew and differentiate into alveolar type 1 (AT1) cells to replenish AT1 cells upon injury (Desai et al, 2014; Barkauskas et al, 2013).”
Endogenous lung stem cells for lung regeneration
McQualter, J. L. (2019) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1596256 · Cited by 20
“Lineage tracing studies of secretory cells, based on the expression of secretoglobin 1A1 (Scgb1a1), have shown that after bleomycin injury or influenza infection, Scgb1a1lineage tagged AT2 and AT1 cells can be observed in the alveolar regions adjacent to the bronchiolar duct [12,14,18,19].”
BackgroundNeonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice
Yee, M., Cohen, E. D., Haak, J., Dylag, A. M., & O’Reilly, M. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-79595-2 · Cited by 20
Tissue Specific DNA Repair Outcomes Shape the Landscape of Genome Editing
Meyenberg, M., da Silva, J. F., & Loizou, J. I. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.728520 · Cited by 21
Development and Functional Characterization of Fetal Lung Organoids
Laube, M., Pietsch, S., Pannicke, T., Thome, U. H., & Fabian, C. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.678438 · Cited by 21
“The use of isolated and defined cell populations and the co-culture of lung epithelial cells with other lung-derived cell types like endothelial cells (10), mesenchymal stem cells (11), and fibroblasts (12), led to the development of self-organizing LOs reflectingmorphological and cellular compositions of bronchial an…”
BackgroundKhan, 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 21
“AT2 cells maintain the alveolar epithelium by their ability to self-renew and they serve as progenitors for AT1 cells [3].”
BackgroundIntermediary 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 19
Egea-Zorrilla, A., Vera, L., Sáez, B., & Pardo–Saganta, A. (2022) · Cells · doi:10.3390/cells11162595 · Cited by 21
“In addition to AT2 cells, considered as primary contributors to post-injury alveolar regeneration, various epithelial progenitor populations have been shown to participate in regeneration after damage [77,78,89].”
BackgroundKonkimalla, A., Konishi, S., Kobayashi, Y., Murthy, P. K. L., Macadlo, L., Mukherjee, A., Elmore, Z. C., Kim, S., Pendergast, A. M., Lee, P. J., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105114 · Cited by 19
Lv, X., Liu, S., Liu, C., Li, Y., Zhang, T., Qi, J., Li, K., Hua, F., Cui, B., Zhang, X., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.01.008 · Cited by 21
Yao, H., Zhu, Y., Lu, H., Ju, H., Xu, S., Qiao, Y., & Wei, S.-J. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110672 · Cited by 20
Dissecting pulmonary fibroblasts heterogeneity in lung development, health and diseases
Zhang, X., Shi, X., Xie, F., Liu, Y., Wei, X., Cai, Y., & Chao, J. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e19428 · Cited by 23
“Researchers find alveolar fibroblasts also express Plin2 and lipoprotein lipase (Lpl), which are general lipofibroblast markers; this is in concordance with previous studies that Pdgfrα+ Tcf21+ alveolar fibroblasts show some phenotypic features of lipofibroblasts [32,56].”
ResultDong, S., Liu, S., Gao, Q., Shi, J., Song, K., Wu, Y., Liu, H., Guo, C., Huang, Y., Du, S., et al. (2023) · Clinical Science · doi:10.1042/cs20230354 · Cited by 20
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 23
“Although PDGFRA + cells were previously shown to be able to support epithelial organoid formation in vitro 15 the exception of ciliated and AT1 cells known to be terminally differentiated.”
BackgroundShao, S., Zhang, N., Specht, G. P., You, S., Song, L., Fu, Q., Huang, D., You, H., Shu, J., Domissy, A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2400077121 · Cited by 22
Breathing new life into the study of COPD with genes identified from genome-wide association studies
Werder, R. B., Zhou, X., Cho, M. H., & Wilson, A. A. (2024) · European Respiratory Review · doi:10.1183/16000617.0019-2024 · Cited by 20
The spatiotemporal cellular dynamics of lung immunity
Lelkes, E., Headley, M. B., Thornton, E. E., Looney, M. R., & Krummel, M. F. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.05.005 · Cited by 20
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
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