Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ wit...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/68049 |
| _version_ | 1811199852631031808 |
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| author | Diptiman Chanda Mohammad Rehan Samuel R Smith Kevin G Dsouza Yong Wang Karen Bernard Deepali Kurundkar Vinayak Memula Kyoko Kojima James A Mobley Gloria A Benavides Victor Darley-Usmar Young-iL Kim Jaroslaw W Zmijewski Jessy S Deshane Stijn De Langhe Victor J Thannickal |
| author_facet | Diptiman Chanda Mohammad Rehan Samuel R Smith Kevin G Dsouza Yong Wang Karen Bernard Deepali Kurundkar Vinayak Memula Kyoko Kojima James A Mobley Gloria A Benavides Victor Darley-Usmar Young-iL Kim Jaroslaw W Zmijewski Jessy S Deshane Stijn De Langhe Victor J Thannickal |
| author_sort | Diptiman Chanda |
| collection | DOAJ |
| description | Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology. |
| first_indexed | 2024-04-12T01:55:25Z |
| format | Article |
| id | doaj.art-ef49c5e79b324a57988570b54d4ab9ff |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:55:25Z |
| publishDate | 2021-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ef49c5e79b324a57988570b54d4ab9ff2022-12-22T03:52:50ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.68049Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cellsDiptiman Chanda0https://orcid.org/0000-0002-4835-4460Mohammad Rehan1Samuel R Smith2Kevin G Dsouza3Yong Wang4Karen Bernard5Deepali Kurundkar6Vinayak Memula7Kyoko Kojima8James A Mobley9Gloria A Benavides10Victor Darley-Usmar11Young-iL Kim12Jaroslaw W Zmijewski13Jessy S Deshane14Stijn De Langhe15https://orcid.org/0000-0003-3867-4572Victor J Thannickal16https://orcid.org/0000-0003-4266-8677Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesJohn W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United States; Department of Surgery, Birmingham, United StatesComprehensive Cancer Center Mass Spectrometry & Proteomics Shared Facility, Birmingham, United StatesDepartment of Anesthesiology and Perioperative Medicine, Birmingham, United StatesDepartment of Pathology, Birmingham, United StatesDepartment of Pathology, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United States; Division of Preventive Medicine, Department of Medicine; University of Alabama at Birmingham, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Birmingham, United StatesJohn W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, United StatesMulticellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology.https://elifesciences.org/articles/68049Agingsenescencemesenchymal stromal cellsepithelial stem cellsoxidative stressregeneration |
| spellingShingle | Diptiman Chanda Mohammad Rehan Samuel R Smith Kevin G Dsouza Yong Wang Karen Bernard Deepali Kurundkar Vinayak Memula Kyoko Kojima James A Mobley Gloria A Benavides Victor Darley-Usmar Young-iL Kim Jaroslaw W Zmijewski Jessy S Deshane Stijn De Langhe Victor J Thannickal Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells eLife Aging senescence mesenchymal stromal cells epithelial stem cells oxidative stress regeneration |
| title | Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells |
| title_full | Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells |
| title_fullStr | Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells |
| title_full_unstemmed | Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells |
| title_short | Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells |
| title_sort | mesenchymal stromal cell aging impairs the self organizing capacity of lung alveolar epithelial stem cells |
| topic | Aging senescence mesenchymal stromal cells epithelial stem cells oxidative stress regeneration |
| url | https://elifesciences.org/articles/68049 |
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