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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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“ATII cells are long-lived cells that self-renew locally (Barkauskas et al., 2013).”
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Wolters, P. J., Blackwell, T. S., Eickelberg, O., Loyd, J. E., Kaminski, N., Jenkins, G., Maher, T. M., Molina-Molina, M., Noble, P. W., Raghu, G., et al. (2018) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30007-9 · Cited by 196
Self-citationLung-on-a-chip: the future of respiratory disease models and pharmacological studies
Shrestha, J., Bazaz, S. R., Es, H. A., Azari, D. Y., Thierry, B., Warkiani, M. E., & Ghadiri, M. (2020) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2019.1710458 · Cited by 206
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BackgroundDirecting traffic: IL ‐17 and IL ‐22 coordinate pulmonary immune defense
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Dye, B. R., Dedhia, P. H., Miller, A. J., Nagy, M. S., White, E. S., Shea, L. D., & Spence, J. R. (2016) · eLife · doi:10.7554/elife.19732 · Cited by 197
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“Lungs were collected, dissociated into single cells (see mouse single-cell derivation in the Meth-ods section ‘Single-cell isolation from tissue samples’), and live (Sytox Blue-negative) GFP + single cells were collected by flow cytometry using a FACS Aria I instrument as previously described 66 .”
MethodZhou, B., Flodby, P., Luo, J., Castillo, D. R., Liu, Y., Yu, F., McConnell, A. M., Varghese, B. A., Li, G., Chimge, N., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci90429 · Cited by 181
Self-citationMitofusins regulate lipid metabolism to mediate the development of lung fibrosis
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Noncanonical WNT-5A signaling impairs endogenous lung repair in COPD
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“Here, we investigated the effects of WNT-5A on ATII cells, which function as progenitor cells in the lung (Barkauskas et al., 2013).”
BackgroundInhibition of LTβR signalling activates WNT-induced regeneration in lung
Conlon, T. M., John-Schuster, G., Heide, D., Pfister, D. R., Lehmann, M., Hu, Y., Ertüz, Z., Lopez, M., Ansari, M., Strunz, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2882-8 · Cited by 185
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Defining Adult Stem Cell Function at Its Simplest: The Ability to Replace Lost Cells through Mitosis
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“However, lineage-tracing of SPC+ AT2 revealed that most of the newly generated AT2 cells were derived from SPC− cells under bleomycin injury, suggesting that other progenitors are involved in distal lung repair [23].”
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“So it appears that the type II cells constitute a population with long-term alveolar stem cells (10, 12, 53) that can self-renew and, in part, differentiate to type I cells; there is some evidence that only a part of this population may be true stem cells (11, 12).”
Wilkinson, D. C., Alva-Ornelas, J. A., Sucre, J. M. S., Vijayaraj, P., Durra, A., Richardson, W., Jonas, S. J., Paul, M. K., Karumbayaram, S., Dunn, B., et al. (2017) · Stem Cells Translational Medicine · doi:10.5966/sctm.2016-0192 · Cited by 165
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Self-citationResolution of Pulmonary Edema. Thirty Years of Progress
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Mitochondrial integrated stress response controls lung epithelial cell fate
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“Recombination in the HopxFlpOERT2/+:SftpcCreERT2:R26RTdTom/+ mice was induced by using 100 μg/g. SI Appendix includes further description of study materials and methods.”
MethodInfluentialRay, S., Chiba, N., Yao, C., Guan, X., McConnell, A. M., Brockway, B., Que, L. G., McQualter, J. L., & Stripp, B. R. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.09.010 · Cited by 146
“…and Barry R. Stripp1,2,* 1Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA 2Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA *Correspondence: barry.stripp@cshs.org http://dx.doi.org/10.1016/j.stemcr.2016.09.010”
BackgroundInfluentialSelf-citationSingle-cell transcriptomic atlas of primate cardiopulmonary aging
Ma, S., Sun, S., Li, J., Fan, Y., Qu, J. T., Sun, L., Wang, S., Zhang, Y., Yang, S., Liu, Z., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00412-6 · Cited by 154
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“These include but are not limited to a role in alveolar Ion transport and fluid balance, innate host defense, and very importantly as a progenitor population for lung repair being capable of both proliferative expansion (self-renewal) and of transdifferentiating to AT1 cells (1, 12, 41, 47, 87).”
BackgroundResultInfluentialSTAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury
Paris, A. J., Hayer, K. E., Oved, J. H., Avgousti, D. C., Toulmin, S. A., Zepp, J. A., Zacharias, W. J., Katzen, J. B., Basil, M. C., Kremp, M. M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0569-x · Cited by 149
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Aspal, M., & Zemans, R. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093188 · Cited by 147
“During homeostasis, alveolar epithelial cells have a long but limited lifespan [1].”
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Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate
Shiraishi, K., Shah, P. P., Morley, M. P., Loebel, C., Santini, G. T., Katzen, J. B., Basil, M. C., Lin, S. M., Planer, J. D., Cantu, E., et al. (2023) · Cell · doi:10.1016/j.cell.2023.02.010 · Cited by 144
A Metabolic Roadmap for Somatic Stem Cell Fate
Ly, C., Lynch, G. S., & Ryall, J. G. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.04.022 · Cited by 144
Farahani, R. H., & Xaymardan, M. (2015) · Stem Cells International · doi:10.1155/2015/362753 · Cited by 143
“The mitogenic activity of the PDGFs on fibroblasts and smooth muscle cells [13] is a well-known fact that led to the discovery of the growth factors.”
BackgroundTracing 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 145
“6,15 We first conducted PNX-induced injury on adult Hopx-CreER;R26-tdT mice (Figure S1A).”
Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis
Xie, T., Liang, J., Liu, N., Huan, C., Zhang, Y., Liu, W., Kumar, M. E., Xiao, R., D'Armiento, J. M., METZGER, D., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85328 · Cited by 139
Self-citationLung cancer stem cells: origin, features, maintenance mechanisms and therapeutic targeting
Heng, W. S., Gosens, R., & Kruyt, F. A. E. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.12.010 · Cited by 138
“In the alveolar space, AEC II cells can proliferate and differentiate into AEC I cells during steady state and mild injury [11].”
BackgroundTGFβ2 and TGFβ3 isoforms drive fibrotic disease pathogenesis
Sun, T., Huang, Z., Liang, W.-C., Yin, J., Lin, W. Y., Wu, J., Vernes, J.-M., Lutman, J., Caplazi, P., Jeet, S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe0407 · Cited by 134
“After ~14 days, spheroids derived from individual AEC2s have developed, with an outer layer of AEC2s and an inner lumen with AEC1s that have differentiated from AEC2 progenitors (15).”
BackgroundMitochondrial dysfunction in lung ageing and disease
Cloonan, S. M., Kim, K., Estèves, P., Trian, T., & Barnes, P. J. (2020) · European Respiratory Review · doi:10.1183/16000617.0165-2020 · Cited by 141
Fgf10 Signaling in Lung Development, Homeostasis, Disease, and Repair After Injury
Yuan, T., Volckaert, T., Chanda, D., Thannickal, V. J., & Langhe, S. D. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00418 · Cited by 130
Finn, J., Sottoriva, K., Pajcini, K. V., Kitajewski, J. K., Chen, C., Zhang, W., Malik, A. B., & Liu, Y. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.046 · Cited by 133
“In addition, AT2 function as facultative stem cells to repair the damaged epithelium (Barkauskas et al., 2013; Desai et al., 2014; Evans et al., 1975).”
InfluentialChronic WNT/β-catenin signaling induces cellular senescence in lung epithelial cells
Lehmann, M., Hu, Q., Hu, Y., Hafner, K., Costa, R., van den Berg, A., & Königshoff, M. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109588 · Cited by 134
“Notably, alveolar epithelial type (AT) II cells secrete surfactant proteins such as Surfactant Protein-C (Sftpc/ SP-C) and serve as progenitor cells for ATI cells, which are indispensable for gas exchange [3,4].”
BackgroundFrom ARDS to pulmonary fibrosis: the next phase of the COVID-19 pandemic?
Michalski, J. E., Kurche, J. S., & Schwartz, D. A. (2021) · Translational research · doi:10.1016/j.trsl.2021.09.001 · Cited by 139
“Type II AECs are considered the stem cell of the distal lung and are responsible for surfactant production and re-epithelization of the bronchoalveolar epithelium after injury.(61) In ARDS, the initial insulting injury results in loss of epithelial barrier function through destruction of the relatively fragile alveola…”
BackgroundShenoy, 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
Transcription factor Etv5 is essential for the maintenance of alveolar type II cells
Zhang, Z., Newton, K., Kummerfeld, S., Webster, J. D., Kirkpatrick, D. S., Phu, L., Eastham‐Anderson, J., Liu, J., Lee, W. P., Wu, J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621177114 · Cited by 126
“A type II (AT2) cells are a stem cell population that self renews and differentiates into alveolar type I (AT1) cells during lung homeostasis or in response to injury (1, 2).”
BackgroundCheng, H., Feng, D., Li, X., Gao, L., Tang, S., Liu, W. Q., Wu, X., Yue, S., Li, C., & Luo, Z. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166204 · Cited by 132
EGF receptor in organ development, tissue homeostasis and regeneration
Tito, C., Masciarelli, S., Colotti, G., & Fazi, F. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01119-9 · Cited by 148
“AT1 cells represent 95% of the peripheral lung surface and are essential for gas exchange; AT2 cells are the precursors of AT1 cells and secrete components of surfactant proteins and regulate the regeneration and repair of lung tissue [217, 218].”
Next generation organoids for biomedical research and applications
Lou, Y., & Leung, A. W. (2017) · Biotechnology Advances · doi:10.1016/j.biotechadv.2017.10.005 · Cited by 138
Wnt and FGF mediated epithelial‐mesenchymal crosstalk during lung development
Volckaert, T., & Langhe, S. D. (2014) · Developmental Dynamics · doi:10.1002/dvdy.24234 · Cited by 135
“Squamous ATI cells make up about 90% of the surface area and are located immediately adjacent to the capillaries, which allows for efficient oxygen and CO2 diffusion, whereas cuboidal ATII cells secrete surfactant to prevent alveolar collapse and have shown to be a bona fide longterm self-renewing stem cell population…”
BackgroundAlveolar progenitor cells and the origin of lung cancer
de Aja, J. S., Dost, A. F. M., & Kim, C. F. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13201 · Cited by 136
Telomere-mediated lung disease
Alder, J. K., & Armanios, M. (2022) · Physiological Reviews · doi:10.1152/physrev.00046.2021 · Cited by 130
Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
Zhang, H., Fillmore Brainson, C., Koyama, S., Redig, A. J., Chen, T., Li, S., Gupta, M., Garcia-de-Alba, C., Paschini, M., Herter-Sprie, G. S., et al. (2017) · Nature Communications · doi:10.1038/ncomms14922 · Cited by 127
“In the alveolar space where gas exchange is carried out by alveolar type I cells, the surfactant-expressing AT2 cells act as stem cells 16,17 .”
Gkatzis, K., Taghizadeh, S., Huh, D., Stainier, D. Y. R., & Bellusci, S. (2018) · European Respiratory Journal · doi:10.1183/13993003.00876-2018 · Cited by 134
Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Hsu, W.-H., LaBella, K. A., Lin, Y., Xu, P., Lee, R., Hsieh, C.-E., Yang, L., Zhou, A., Blecher, J. M., Wu, C.-J., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1467 · Cited by 125
Lung Pericytes and Resident Fibroblasts
Barron, L., Gharib, S. A., & Duffield, J. S. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.07.004 · Cited by 132
Recent advances in lung organoid development and applications in disease modeling
Vazquez‐Armendariz, A. I., & Tata, P. R. (2023) · Journal of Clinical Investigation · doi:10.1172/jci170500 · Cited by 136
“In contrast, stimulation of lung progenitor cells with DCI, FGF, and CHIR leads to the formation of alveolar organoids comprising AEC1s and AEC2s (27, 61).”
BackgroundMethodInfluentialMitochondrial Dysfunction in Lung Pathogenesis
Piantadosi, C. A., & Suliman, H. B. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034322 · Cited by 124
Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis
Parimon, T., Hohmann, M. S., & Yao, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126214 · Cited by 123
“AT2 cell cellular senescence in pulmonary fibrosis AT2 cell, a facultative stem cell that produces and secrets pulmonary surfactant in its quiescent state, is considered to be the progenitor cell responsible for normal maintenance of the alveolar epithelium [48].”
BackgroundQuantius, 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 126
“However, our data do not fully exclude contribution of an AEC II progenitor to the alveolar regeneration process, as demonstrated for bleomycin-induced damage [33], particularly as AECII constitute a highly abundant cell population of the lung, and even a small proliferating AECII fraction could still contribute to ep…”
BackgroundFgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells
Volckaert, T., Yuan, T., Chao, C., Bell, H. W., Sitaula, A., Szimmtenings, L., Agha, E. E., Chanda, D., Majka, S. M., Bellusci, S., et al. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.09.003 · Cited by 121
“, 2009), and give rise to alveolar epithelial cells after major lung epithelial injuries (Barkauskas et al., 2013; Kim et al., 2005; Lee et al., 2014).”
BackgroundAn SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis
Katzen, J. B., Wagner, B. D., Venosa, A., Kopp, M. C., Tomer, Y., Russo, S. J., Headen, A. C., Basil, M. C., Stark, J. M., Mulugeta, S., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126125 · Cited by 120
“However the 20%–30% decline in AT2 cell number we observed in this model at 4 weeks after tamoxifen treatment was a degree of apoptosis found to be insufficient to induce spontaneous fibrosis in multiple AT2 cell ablation models (73, 74).”
BackgroundMulugeta, S., Nureki, S., & Beers, M. F. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00139.2015 · Cited by 124
“The health of the distal lung relies on the proper function of AT2 cells, which play a critical role in the production and maintenance of pulmonary surfactant, contribute to overall barrier function, perform xenobiotic metabolism, and participate in lung repair serving as a progenitor population following lung injury…”
BackgroundThe biology of the ABCA3 lipid transporter in lung health and disease
Beers, M. F., & Mulugeta, S. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2554-z · Cited by 118
“…being crucial to the general health of the distal lung, participating in lung repair by serving as a progenitor cell population for the replacement of long-lived AT2 and type 1 epithelial (AT1) cells following lung injury (Adamson and Bowden 1975; Barkauskas et al. 2013; Spencer and Shorter 1962).”
Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis
Cao, Z., Ye, T., Sun, Y., Ji, G., Shido, K., Chen, Y., Luo, L., Na, F., Li, X., Huang, Z., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai8710 · Cited by 121
“S1A) (14, 21, 24, 26), and livers were grafted with hepatocytes mediating hepatic reconstitution (Fig.”
MethodCarcaterra, M., & Caruso, C. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.110412 · Cited by 122
“during lung injury, a process carried out by progenitors for AEC-I cells [16].”
New Insights into Hippo/YAP Signaling in Fibrotic Diseases
Mia, M. M., & Singh, M. K. (2022) · Cells · doi:10.3390/cells11132065 · Cited by 120
“AT2 cells act as stem/progenitor cells that are capable of self-renewal and differentiation into AT1 cells during both homeostatic state and reparative phase post-injury [50].”
BackgroundFra-2–expressing macrophages promote lung fibrosis
Ucero, A. C., Bakiri, L., Roediger, B., Suzuki, M., Jiménez, M., Mandal, P., Braghetta, P., Bonaldo, P., Paz-Ares, L. G., Torre, C. F., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci125366 · Cited by 123
“Immunohistological analysis of prefibrotic (before structural changes; at 6 weeks old) and fibrotic (17 weeks) Fra-2Tg lungs revealed that Fra-2 protein was detectable in mesenchymal cells expressing vimentin, in cells of the monocyte/macrophage lineage expressing colony-stimulating factor 1 receptor (Csf-1r), and in…”
BackgroundEpithelial 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 119
Dial, C. F., Tune, M. K., Doerschuk, C. M., & Mock, J. R. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0019oc · Cited by 117
“The paradigm for alveolar epithelial repair has been that AT1 cells are damaged and AT2 cells undergo hyperplasia, cell spreading, and proliferation at sites of injury to reestablish an intact functional epithelial barrier for gas exchange (10, 44, 45).”
BackgroundAlysandratos, K., Russo, S. J., Petcherski, A., Taddeo, E. P., Acín‐Pérez, R., Villacorta-Martín, C., Jean, J., Mulugeta, S., Rodríguez, L. R., Blum, B. C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109636 · Cited by 116
“, 2007), particularly in the absence of mesenchymal feeders (Barkauskas et al., 2013).”
Liberti, D. C., Kremp, M. M., Liberti, W. A., Penkala, I. J., Li, S., Zhou, S., & Morrisey, E. E. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109092 · Cited by 115
“Lung alveolar organoid assay— Organoid assays were performed as previously described with modification (Barkauskas et al., 2013; Frank et al., 2016; Peng et al., 2015; Zacharias et al., 2018; Zepp et al., 2017).”
Influential3D and organoid culture in research: physiology, hereditary genetic diseases and cancer
Suarez-Martinez, E., Suazo-Sanchez, I., Celis-Romero, M., & Carnero, A. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00775-w · Cited by 118
“AEC2-derived organoids, called ‘alveolospheres’, contain both AEC2 and AEC1 present in the alveoli but are not yet fully defined and need the presence of lung stromal cells for growth and differentiation [102].”
BackgroundTwo nested developmental waves demarcate a compartment boundary in the mouse lung
Alanis, D. M., Chang, D. R., Akiyama, H., Krasnow, M. A., & Chen, J. (2014) · Nature Communications · doi:10.1038/ncomms4923 · Cited by 113
Idiopathic Pulmonary Fibrosis: From Epithelial Injury to Biomarkers - Insights from the Bench Side
Kolb, Borensztajn, K., Crestani, B., & Kolb, M. R. J. (2013) · Respiration · doi:10.1159/000357598 · Cited by 114
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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