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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 601–700 of 1,000
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Rippa, A. L., Алпеева, Е. В., Vasiliev, A. V., & Vorotelyak, E. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212107 · Cited by 31
Development of human alveolar epithelial cell models to study distal lung biology and disease
Tran, E., Shi, T., Li, X., Chowdhury, A. Y., Du, J., Liu, Y., Wang, H., Yan, C., Wallace, W. D., Lu, R., et al. (2022) · iScience · doi:10.1016/j.isci.2022.103780 · Cited by 34
“For each flank, a master mix of cells resuspended in sterile phosphate-buffered saline (PBS) and 50% final concentration of Matrigel MembraneMatrix solution (Corning 354234) was prepared such that 13 106 cells were delivered in 150 mL of solution.”
BackgroundInfluentialAbnormal 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
“Using a Sftpc+ ATII depletion mouse model, it was concluded that there are more Sftpc+ ATII cells derived from alveolar ATII cells than from BASCs [15].”
BackgroundResultInfluentialSelf-citationGao, F., Li, C., Danopoulos, S., Alam, D. A., Peinado, N., Webster, S., Borok, Z., Kohbodi, G. A., Bellusci, S., & Minoo, P. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110608 · Cited by 31
“3D alveolar organoid culture—3D alveolar organoid assays were performed as originally described (Barkauskas et al., 2013) with some modifications.”
BackgroundMethodHansen, S., Zhang, Y., Hwang, S., Nabhan, A. N., Li, W., Fuhrmann, J., Kschonsak, Y. T., Zhou, L., Nile, A. H., Gao, X., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2207327119 · Cited by 30
“We modeled alveolar regeneration using the alveolosphere model, in which AT2 cells were cocultured with stromal cells that provided paracrine signals activating AT2 stem cell activity (64) (Fig.”
MethodAntifibrotic effects of sodium-glucose cotransporter-2 inhibitors: A comprehensive review
Shakour, N., Karami, S., Iranshahi, M., Butler, A. E., & Sahebkar, A. (2023) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2023.102934 · Cited by 32
Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell–Specific Genes
Marconett, C. N., Zhou, B., Sunohara, M., Pouldar, T. M., Wang, H., Liu, Y., Rieger, M. E., Tran, E., Flodby, P., Siegmund, K. D., et al. (2016) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0071oc · Cited by 31
Isolation and characterisation of alveolar type II pneumocytes from adult bovine lung
Lee, D., Salguero, F. J., Grainger, D., Francis, R. J., MacLellan‐Gibson, K., & Chambers, M. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-30234-x · Cited by 31
Yudhawati, R., Amin, M., Rantam, F. A., Prasetya, R. R., Dewantari, J. R., Nastri, A. M., Poetranto, E. D., Wulandari, L., Lusida, M. I., Koesnowidagdo, S., et al. (2020) · BMC Infectious Diseases · doi:10.1186/s12879-020-05525-2 · Cited by 30
“Type II alveolar epithelial cells can renew themselves and act as progenitor cells for type I alveola epithelial cells during normal homeostatic as well as after epithelial damage due to injury [29].”
BackgroundAdvances in cellular senescence in idiopathic pulmonary fibrosis (Review)
Han, S., Lu, Q., & Liu, X. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.11844 · Cited by 32
“ATⅡ cells function as alveolar progenitors and long‑term stem cells in the adult lung (82).”
Chimenti, I., Pagano, F., Angelini, F., Siciliano, C., Mangino, G., Picchio, V., FALCO, E. D., Peruzzi, M., Carnevale, R., Ibrahim, M., et al. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0374 · Cited by 30
“Isolation of different mesenchymal or epithelial populations of resident lung progenitor cells (LPCs) has been described by multiple protocols and criteria, with only few of them having been successfully applied to healthy human lung tissue [9] [10] [11] [12] [13] [14] , and with remaining uncertainty about the best m…”
Claudin-18: unexpected regulator of lung alveolar epithelial cell proliferation
Kotton, D. N. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99799 · Cited by 30
“For example, FGF, Wnt, activated KRAS, and, most recently, YAP signaling have all been reported to promote alveolar epithelial cell proliferation (4–9).”
Shiraishi, K., Nakajima, T., Shichino, S., Deshimaru, S., Matsushima, K., & Ueha, S. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.05.187 · Cited by 30
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 31
Weng, A., Maciel, M., Watanabe, S., Welch, L. C., Flozak, A. S., Grant, R. A., Aillon, R. P., Dada, L. A., Han, S., Hinchcliff, M., et al. (2022) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2021-0356oc · Cited by 30
Contribution of Trp63CreERT2-labeled cells to alveolar regeneration is independent of tuft cells
Huang, H., Jiang, M., Zhang, Y., Biermann, J., Melms, J. C., Danielsson, J. A., 方银善, Yang, Y., Qiang, L., Liu, J., et al. (2022) · eLife · doi:10.7554/elife.78217 · Cited by 30
“At 18 dpi mouse peripheral lungs were dissected and dissociated according to the protocol as previously described ( Barkauskas et al., 2013 ; Rock et al., 2011 ). tdT + cells were sorted by FACS and cultured using the protocol as previously reported ( Mou et al., 2016 ), and the protocol for…”
Huang, G., Liang, J., Huang, K. Y., Liu, X., Taghavifar, F., Yao, C., Parimon, T., Liu, N., Dai, K., Aziz, A. W., et al. (2022) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2022-0074oc · Cited by 31
Self-citationDirected differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme
Alber, A. B., Marquez, H. A., Ma, L., Kwong, G., Thapa, B. R., Villacorta-Martín, C., Lindstrom-Vautrin, J., Bawa, P., Wang, F., Luo, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39099-9 · Cited by 31
Stem Cells and Their Mediators – Next Generation Therapy for Bronchopulmonary Dysplasia
Möbius, M. A., & Thébaud, B. (2015) · Frontiers in Medicine · doi:10.3389/fmed.2015.00050 · Cited by 30
“In vitro approaches might involve the ability of MSCs to support the generation of alveolospheres out of murine alveolar type II cells in 3D organoid culture systems (108).”
BackgroundRespiratory Tissue Engineering: Current Status and Opportunities for the Future
O’Leary, C., Gilbert, J. L., O’Dea, S., O’Brien, F. J., & Cryan, S. (2015) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2014.0525 · Cited by 30
“58 This new study builds on that of Rock et al. 57 by showing that in addition to their propensity to repopulate the alveolar region following bleomycin administration, these cells have clonal properties with long-term self-renewal described for over a year.”
Ye, W., Chen, C., Gao, Y., Zheng, Z.-S., Xu, Y., Yun, M., Weng, H.-W., Xie, D., Ye, S., & Zhang, J. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.13 · Cited by 30
3D culture models for studying branching morphogenesis in the mammary gland and mammalian lung
Nerger, B. A., & Nelson, C. M. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.08.043 · Cited by 29
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
Organoids as preclinical models of human disease: progress and applications
Chen, B., Du, C., Wang, M., Guo, J., & Liu, X. (2024) · Medical Review · doi:10.1515/mr-2023-0047 · Cited by 31
“To generate ‘ alveolospheres ’ , a lineage-tracing approach was initially employed [54].”
MethodLiang, J., Huang, G., Liu, X., Zhang, X., Rabata, A., Liu, N., Fang, K., Taghavifar, F., Dai, K., Kulur, V., et al. (2024) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2023-0290oc · Cited by 29
“Type 2 alveolar epithelial cells (AEC2s) function as progenitor cells that maintain epithelial homeostasis and repair damaged epithelium after lung injury (3, 6 – 9).”
BackgroundSelf-citationSystematic review of drug effects in humans and models with surfactant-processing disease
Klay, D., Hoffman, T. W., Harmsze, A. M., Grutters, J. C., & van Moorsel, C. H. M. (2018) · European Respiratory Review · doi:10.1183/16000617.0135-2017 · Cited by 29
Guo, L., Karoubi, G., Duchesneau, P., Aoki, F. G., Shutova, M. V., Rogers, I. M., Nagy, A., & Waddell, T. K. (2018) · npj Regenerative Medicine · doi:10.1038/s41536-018-0052-5 · Cited by 29
The role of pulmonary mesenchymal cells in airway epithelium regeneration during injury repair
Fang, S., Zhang, S., Dai, H., Hu, X., Li, C., & Xing, Y. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1452-1 · Cited by 31
Assessing Human Airway Epithelial Progenitor Cells for Cystic Fibrosis Cell Therapy
Lee, R. E., Miller, S. M., Mascenik, T., Lewis, C. A., Dang, H., Boggs, Z. H., Tarran, R., & Randell, S. H. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0384oc · Cited by 29
Self-citationSingle‐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
Role and mechanisms of autophagy in lung metabolism and repair
Li, X., Zhao, F., Wang, A., Cheng, P., & Chen, H. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03841-7 · Cited by 30
“Previous data showed that AT2 cells proliferate and give rise to AT1 cells to restore the alveolar epithelium during bleomycin injury [15, 18, 19], and thus the cells are considered as alveolar stem/progenitor cells [15, 94].”
BackgroundHuman cell receptors: potential drug targets to combat COVID-19
Raghav, P. K., Kalyanaraman, K., & Kumar, D. (2021) · Amino Acids · doi:10.1007/s00726-021-02991-z · Cited by 29
Riccetti, M., Ushakumary, M. G., Waltamath, M., Green, J., Snowball, J. M., Dautel, S. E., Endale, M., Lami, B., Woods, J. C., Ahlfeld, S. K., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.152404 · Cited by 29
“MANCs and PDGFRA+ fibroblasts are known to support the alveolar niche in adult lungs and have been shown to support AT2-to-AT1 transdifferentiation in lung organoid cultures (10, 73, 74).”
Weiss, D. J., Chambers, D. C., Giangreco, A., Keating, A., Kotton, D. N., Lelkes, P. I., Wagner, D. E., & Prockop, D. J. (2015) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201502-086st · Cited by 30
HOPX: A Unique Homeodomain Protein in Development and Tumor Suppression
Gokulan, R. C., Yap, L. F., & Paterson, I. C. (2022) · Cancers · doi:10.3390/cancers14112764 · Cited by 29
Oatis, D. A., Simon-Repolski, E., Baltă, C., Mihu, A. G., Pieretti, G., Alfano, R., Peluso, L., Trotta, M. C., D’Amico, M., & Hermenean, A. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158210 · Cited by 30
“and stabilization of the airway epithelial barrier; they are also involved in the immunedefense processes during lung injury and differentiation into type I alveolar epithelial cells to promote tissue repair [13,14].”
BackgroundELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19
Pietzner, M., Chua, R. L., Wheeler, E., Jechow, K., Willett, J., Radbruch, H., Trump, S., Heidecker, B., Zeberg, H., Heppner, F. L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31999-6 · Cited by 30
“As cells with stem-like capacity, they are involved in the maintenance and repair of their respective cellular niches 49,69 .”
Lung regeneration and translational implications of the postpneumonectomy model
Thane, K. E., Ingenito, E. P., & Hoffman, A. M. (2013) · Translational research · doi:10.1016/j.trsl.2013.11.010 · Cited by 29
Fujimoto, J., Nunomura‐Nakamura, S., Liu, Y., Lang, W., McDowell, T. L., Jakubek, Y. A., Ezzeddine, D., Ochieng, J. K., Petersen, J. L., Davies, G., et al. (2017) · International Journal of Cancer · doi:10.1002/ijc.30851 · Cited by 30
“Also, AT2 cell ablation was found to induce self-renewal (duplication) of remaining AT2 cells.(52) The recent report by Desai et al.”
BackgroundDas, D., Fletcher, R. B., & Ngai, J. (2019) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.361 · Cited by 29
“Furthermore, lineage-traced AT2 cells give rise to AT1 cells at a low rate in homeostasis (Barkauskas et al., 2013; Nabhan, Brownfield, Harbury, Krasnow, & Desai, 2018; Zacharias et al., 2018), but a subset of AT2 cells can regenerate both alveolar epithelial cell types following injury (Barkauskas et al.”
BackgroundInfluentialCell-by-Cell Deconstruction of Stem Cell Niches
Tikhonova, A. N., Lasry, A., Austin, R. J., & Aifantis, I. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.06.013 · Cited by 34
“A small subset of AT2 cells act as respiratory SCs (Barkauskas et al., 2013), giving rise to all alveolar cells in the respiratory epithelium, yet the signals distinguishing AT2 SCs from bulk AT2 cells are not fully understood.”
BackgroundSchmidt, M., Cattani-Cavalieri, I., Nuñez, F. J., & Ostrom, R. S. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.05.002 · Cited by 30
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
Maier, B. B., Hladik, A., Lakovits, K., Korosec, A., Martins, R., Kral-Pointner, J. B., Mesteri, I., Strobl, B., Müller, M. M., Kalinke, U., et al. (2016) · European Journal of Immunology · doi:10.1002/eji.201546201 · Cited by 30
CD44highalveolar type II cells show stem cell properties during steady-state alveolar homeostasis
Chen, Q., Kumar, V. S., Finn, J., Jiang, D., Liang, J., Zhao, Y., & Liu, Y. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00564.2016 · Cited by 28
The Lung and Esophagus: Developmental and Regenerative Overlap
Morrisey, E. E., & Rustgi, A. K. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.007 · Cited by 28
“Previous work has indicated that there is plasticity between these two lineages; however, what functional role this plasticity plays in regeneration of the gas-exchange interface in the lung is unknown [34,35].”
BackgroundZhang, D., Wu, L., Du, Y., Zhu, Y., Pan, B., Xue, X., & Fu, J. (2018) · Pediatric Pulmonology · doi:10.1002/ppul.24047 · Cited by 28
“AT-II cells thus play an important role in alveolarization and alveolar injury repair as alveolar stem cells.(24,25) Many studies have shown that levels of apoptosis are elevated in BPD, and that this increased apoptosis levels has a crucial effect on alveolar maldevelopment in BPD.”
BackgroundAccelerated lung aging and chronic obstructive pulmonary disease
Yoon, Y.-S., Jin, M., & Sin, D. D. (2019) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2019.1580576 · Cited by 26
“In the distal lung, alveolar type II cells have the regenerative capacity to differentiate into alveolar type I cells [110].”
BackgroundTranslating Basic Research into Safe and Effective Cell-based Treatments for Respiratory Diseases
Ikonomou, L., Wagner, D. E., Turner, L. G., & Weiss, D. J. (2019) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201812-890cme · Cited by 30
Fysikopoulos, A., Seimetz, M., Hadžić, S., Knoepp, F., Wu, C., Malkmus, K., Wilhelm, J., Pichl, A., Bednorz, M., Roxlau, E. T., et al. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15057 · Cited by 28
Heng, W. S., Kruyt, F. A. E., & Cheah, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115697 · Cited by 33
“AEC I and AEC II cells are restricted to the alveolar space [9,15].”
BackgroundMarega, M., Chen, C., & Bellusci, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.656883 · Cited by 28
“During this time frame, organoids are formed which are made of SftpcPos-AT2 cells as well as PodoplaninPos-AT1 cells (Barkauskas et al., 2013).”
BackgroundInfluentialGüney, T. G., Herranz, A. M., Mumby, S. E., Dunlop, I. E., & Adcock, I. M. (2021) · iScience · doi:10.1016/j.isci.2021.103061 · Cited by 31
“Monolayer cultures of airway epithelium are ineffective in modeling disease reflecting the differences by which primary human cells interact with each other and how they communicate within the airway 3-dimensional (3D) structure (Gkatzis et al., 2018; Barkauskas et al., 2013).”
BackgroundExtracellular vesicle-mediated cellular crosstalk in lung repair, remodelling and regeneration
Kadota, T., Fujita, Y., Araya, J., Ochiya, T., & Kuwano, K. (2022) · European Respiratory Review · doi:10.1183/16000617.0106-2021 · Cited by 33
Tóth, A., Steinmeyer, S. H., Kannan, P. S., Gray, J. K., Jackson, C. M., Mukherjee, S., Demmert, M., Sheak, J. R., Benson, D., Kitzmiller, J. A., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abl8574 · Cited by 29
Liberti, D. C., Liberti, W. A., Kremp, M. M., Penkala, I. J., Cardenas‐Diaz, F. L., Morley, M. P., Babu, A., Zhou, S., Fernandez, R. J., & Morrisey, E. E. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.06.007 · Cited by 28
Human alveolar progenitors generate dual lineage bronchioalveolar organoids
Hoffmann, K., Obermayer, B., Hönzke, K., Fatykhova, D., Demir, Z., Löwa, A., Alves, L. G. T., Wyler, E., López-Rodríguez, E., Mieth, M., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03828-5 · Cited by 28
Embryology and anatomy of congenital diaphragmatic hernia
Leon, N. D., Tse, W. H., Ameis, D., & Keijzer, R. (2022) · Seminars in Pediatric Surgery · doi:10.1016/j.sempedsurg.2022.151229 · Cited by 30
Lung development and regeneration: newly defined cell types and progenitor status
Meng, X., Cui, G., & Peng, G. (2023) · Cell Regeneration · doi:10.1186/s13619-022-00149-0 · Cited by 28
“Of note, AT2 cells also act as progenitors in alveoli, which can self-renew and differentiate into AT1 cells during lung development and regeneration (Barkauskas et al. 2013; Frank et al. 2016).”
BackgroundFunctional Pdgfra fibroblast heterogeneity in normal and fibrotic mouse lung
Trempus, C. S., Papas, B. N., Sifre, M. I., Bortner, C. D., Scappini, E., Tucker, C. J., Xu, X., Johnson, K. L., Deterding, L. J., Williams, J. G., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.164380 · Cited by 30
“JCI Insight 2023;8(22):e164380 https://doi.org/10.1172/jci.insight.164380 (LipoFBs, a subpopulation of Pdgfra + FBs) are an indispensable constituent of the alveolar stem cell niche, where they are required for both alveolar homeostasis and epithelial regeneration after injury (9–12).”
BackgroundMethodInfluentialInfection of mice with influenza A/WSN/33 (H1N1) virus alters alveolar type II cell phenotype
Hofer, C. C., Woods, P. S., & Davis, I. C. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00373.2014 · Cited by 28
“New therapeutics that can promote ATII cell survival and increase surfactant lipid and protein synthesis are therefore likely to be of benefit in patients with influenza-induced ALI.”
BackgroundInfluentialLee, S., Lim, J., Lee, J.-H., Ju, H., Heo, J., Kim, Y., Kim, S., Yu, H. Y., Ryu, C., Lee, S., et al. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7743 · Cited by 28
Nizamoglu, M., Joglekar, M. M., Almeida, C. R., Larsson‐Callerfelt, A., Dupin, I., Guenat, O. T., Henrot, P., van Os, L., Otero, J., Elowsson, L., et al. (2023) · European Respiratory Review · doi:10.1183/16000617.0042-2023 · Cited by 33
Wang, B., Gao, Y., Sun, L., Xue, M., Wang, M., Zhang, Z., Zhang, L., & Zhang, L. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122404 · Cited by 27
Pan, X., Wang, L., Yang, J., Li, Y., Xu, M., Liang, C., Liu, L., Li, Z., Xia, C., Pang, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52827-z · Cited by 31
“Most importantly, AT2 cells serve as local progenitor cells for AT1 cells, facilitating alveolar epithelial turnover through precisely coordinated proliferation and differentiation 5,10,11 .”
Zhu, Z., Cheng, Y., Liu, X., Ding, W., Liu, J., Ling, Z., & Wu, L. (2025) · Cell Transplantation · doi:10.1177/09636897241303271 · Cited by 31
A host-pathogen metabolic synchrony that facilitates disease tolerance
Chen, Y.-T., Lohia, G. K., Chen, S., Liu, Z., Lung, T. W. F., Wang, C., & Riquelme, S. A. (2025) · Nature Communications · doi:10.1038/s41467-025-59134-1 · Cited by 27
“6g), and compensatory type 2 pneumocyte hyperplasia to replenish them in the lung tissue 78,79 (Fig.”
Arai, D., Hegab, A., Soejima, K., Kuroda, A., Ishioka, K., Yasuda, H., Naoki, K., Kagawa, S., Hamamoto, J., Yin, Y.-J., et al. (2014) · Journal of Pathology · doi:10.1002/path.4486 · Cited by 25
“Lung fibroblasts are essential for distal lung progenitor/stem cell growth and regeneration [17,42] and FGF10 has been suggested to be a major regulator of these processes [17,43].”
BackgroundPleural Hypercarbia After Lung Surgery Is Associated With Persistent Alveolopleural Fistulae
Bharat, A., Graf, N., Mullen, A., Kanter, J. A., Andrei, A., Sporn, P. H. S., DeCamp, M. M., & Sznajder, J. I. (2015) · CHEST Journal · doi:10.1378/chest.15-1591 · Cited by 27
The renin angiotensin system in liver and lung: impact and therapeutic potential in organ fibrosis
Uhal, B. D., Abdul‐Hafez, A., Mohamed, T., Omar, H., & Shemis, M. A. (2018) · Journal of Lung Pulmonary & Respiratory Research · doi:10.15406/jlprr.2018.05.00160 · Cited by 27
Sala, F. D., di Gennaro, M., Lista, G., Messina, F., Ambrosio, L., & Borzacchiello, A. (2021) · Polymers · doi:10.3390/polym13172928 · Cited by 27
“ATII cells represent the primary target of external injury in the lung and a key lineage in the repair process critical for reestablishment of normal pulmonary function [16].”
BackgroundYang, M., Park, M.-J., Lee, J., Oh, B., Kang, K. W., Kim, Y., Lee, S., Lim, J., Jung, T.-Y., Park, J., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.010 · Cited by 30
“In addition, AT2 cells serve as alveolar stem cells that can differentiate into AT1 cells, suggesting the pivotal role of AT1 and AT2 cells in lung homeostasis.(9)”
iPSC-derived mesenchymal cells that support alveolar organoid development
Tamai, K., Sakai, K., Yamaki, H., Moriguchi, K., Igura, K., Maehana, S., Suezawa, T., Takehara, K., Hagiwara, M., Hirai, T., et al. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2022.100314 · Cited by 27
“Although WNT5A, FGF7, and PDGFRA are important factors in AT2 cells (Barkauskas et al., 2013; Nabhan et al., 2018; Zepp et al., 2017), they were up-regulated in HDFs.”
BackgroundResultInfluentialMyronenko, O., Foris, V., Crnković, S., Olschewski, A., Rocha, S., Nicolls, M. R., & Olschewski, H. (2023) · European Respiratory Review · doi:10.1183/16000617.0173-2022 · Cited by 28
Rational engineering of lung alveolar epithelium
Leiby, K. L., Yuan, Y., Ng, R., Raredon, M. S. B., Adams, T. S., Baevova, P., Greaney, A. M., Hirschi, K. K., Campbell, S. G., Kaminski, N., et al. (2023) · npj Regenerative Medicine · doi:10.1038/s41536-023-00295-2 · Cited by 26
How do K-RAS-activated cells evade cellular defense mechanisms?
Lee, Y.-S., & Bae, S.-C. (2015) · Oncogene · doi:10.1038/onc.2015.153 · Cited by 27
Oligohydramnios compromises lung cells size and interferes with epithelial–endothelial development
Najrana, T., Ramos, L. M., Eid, R. A., & Sanchez‐Esteban, J. (2017) · Pediatric Pulmonology · doi:10.1002/ppul.23662 · Cited by 28
“Type II epithelial cells are capable of differentiating into type I cells upon lung injury after birth.(36,37) However, this compensatory effect does not occur prenatally, and the population of type I cells are derived only from bipotent progenitor cells.”
BackgroundShared epithelial pathways to lung repair and disease
Σπέλλα, Μ., Lilis, I., & Stathopoulos, G. T. (2017) · European Respiratory Review · doi:10.1183/16000617.0048-2017 · Cited by 27
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
Auld, S. C., Sheshadri, A., Alexander‐Brett, J. M., Aschner, Y., Barczak, A. K., Basil, M. C., Cohen, K. A., Cruz, C. S. D., McGroder, C. F., Restrepo, M. I., et al. (2024) · Annals of the American Thoracic Society · doi:10.1513/annalsats.202406-651st · Cited by 28
“The degree of alveolar damage determines how robust a regenerative response is required for barrier restoration (36, 225), but it also relates to the severity of an “ aberrant basaloid ” injury response that may occur.”
Eiken, M. K., Childs, C. J., Brastrom, L. K., Frum, T., Plaster, E. M., Ahmed, D. W., Spencer, R. C., Shachaf, O., Pfeiffer, S., Levine, J. E., et al. (2024) · Stem Cell Reports · doi:10.1016/j.stemcr.2024.11.006 · Cited by 28
Li, L., Wu, P., Wei, Y., Lü, M., Ge, H., Wang, P., Sun, J., Horng, T., Liu, X., Shen, X., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2024.115220 · Cited by 32
Hoffman, E. T., Shah, A., Barboza, W. R., Rodríguez, L. R., Dherwani, R., Dooley, P. E., Minakin, K., Tomer, Y., Ayers, L. J., Jones, D. L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63735-1 · Cited by 32
“Mouse lung co-culture organoids were formed according to previously established protocols 64 .”
Theratyping in cystic fibrosis
Crawford, K. J., & Downey, D. G. (2018) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000521 · Cited by 26
Targeted regulation of fibroblast state by CRISPR-mediated CEBPA expression
Liu, W. Q., Meridew, J. A., Aravamudhan, A., Ligresti, G., Tschumperlin, D. J., & Tan, Q. (2019) · Respiratory Research · doi:10.1186/s12931-019-1253-1 · Cited by 26
Targeting p16INK4a Promotes Lipofibroblasts and Alveolar Regeneration after Early-Life Injury
Zysman, M., Baptista, B. R., Essari, L.-A., Taghizadeh, S., de Ménonville, C. T., Giffard, C., Issa, A., Franco‐Montoya, M., Breau, M., Souktani, R., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201908-1573oc · Cited by 28
Repurposing A549 Adenocarcinoma Cells: New Options for Drug Discovery
de Alba, C. G. (2021) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2021-0048ed · Cited by 25
“AT2 cells also serve as facultative progenitor cells that regenerate the lung alveoli after injury or during normal attrition (12).”
BackgroundZhu, Y., Pu, Q., Zhang, Q., Liu, Y., Ma, Y., Yuan, Y., Liu, L., & Zhu, W. (2023) · Cancer Medicine · doi:10.1002/cam4.6309 · Cited by 25
Development of Lung Epithelium from Induced Pluripotent Stem Cells
Ghaedi, M., Niklason, L. E., & Williams, J. C. (2015) · Current Transplantation Reports · doi:10.1007/s40472-014-0039-0 · Cited by 26
Therapeutic Targeting of IL-11 for Chronic Lung Disease
Kortekaas, R. K., Burgess, J. K., van Orsoy, R., Lamb, D. J., Webster, M. J., & Gosens, R. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.01.007 · Cited by 26
“Additionally, AT2 cells are thought to function as progenitor cells in the adult lung, which can give rise to AT1 cells [61].”
BackgroundPreclinical Models for the Study of Lung Cancer Pathogenesis and Therapy DevelopmentPreprint
Estape, A. A., Foggetti, G., Starrett, J. H., Nguyen, D. X., & Politi, K. A. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a037820 · Cited by 23
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 31
Mižíková, I., & Thébaud, B. (2023) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-023-00158-2 · Cited by 29
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 27
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 28
England, F. J., Bordeu, I., Ng, M.-E., Bang, J., Kim, B., Choi, J., Cardoso, E. C., Koo, B., Simons, B. D., & Lee, J. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.01.011 · Cited by 26
“7,8 These cells display functional heterogeneity during lung regeneration 8–11 , but due to the slow steady-state turnover of the alveolar epithelium, it remains unclear how distinct AT2 subpopulations function in unison to maintain the stem cell pool and contribute towards their alveolar type I…”
Ozdemir, S. A., Faizan, M. I., Kaur, G., Shaikh, S. B., Islam, K. U., & Rahman, I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199687 · Cited by 28
Wang, X., Sha, X.-L., Li, Y., Li, C., Chen, S.-H., Wang, J.-J., & Xia, Z. (2020) · BMC Anesthesiology · doi:10.1186/s12871-020-01089-5 · Cited by 26
Horie, M., Castaldi, A., Sunohara, M., Wang, H., Ji, Y., Liu, Y., Li, F., Wilkinson, T. A., Hung, L. T., Shen, H. M., et al. (2020) · Cells · doi:10.3390/cells9112460 · Cited by 23
“Aquaporin 5 (AQP5), podoplanin (PDPN), homeodomain-only protein (HOPX) and more recently advanced glycation end products receptor (AGER) have been viewed as ‘classical’ AT1 cell markers [4,14].”
BackgroundAGO2 promotes tumor progression in KRAS-driven mouse models of non–small cell lung cancer
Tien, J. C.-Y., Chugh, S., Goodrum, A. E., Cheng, Y., Mannan, R., Zhang, Y., Wang, L., Dommeti, V. L., Wang, X., Xu, A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2026104118 · Cited by 25
“…mechanism by which AGO2 induces NSCLC progression in the KPC model. miR-214 — a species for which both oncogenic and To further dissect the mechanistic link between AGO2 and canonical KRAS signaling in this system, we dissociated KPC tumor nodules and cultured cells ex vivo as organoids (41, 42).”
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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