P. Kramer, V. Ho, C. Bowden, N. Ronaghan, U. Pena, D. Rowbotham, T. Brown, M. Tellis, J. Finn, A.Y. Yoshikawa, A. Eaves, S. Louis, W. Chang, J. Hou
{"title":"Highly Expandable Human Alveolar Organoids to Study Respiratory Diseases","authors":"P. Kramer, V. Ho, C. Bowden, N. Ronaghan, U. Pena, D. Rowbotham, T. Brown, M. Tellis, J. Finn, A.Y. Yoshikawa, A. Eaves, S. Louis, W. Chang, J. Hou","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3627","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3627","url":null,"abstract":"Organoids are emerging to be an excellent tool for studying human development and disease. The COVID-19 pandemic has highlighted the importance of physiologically relevant alveolar infection models that include both alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. To address the need for an alveolar organoid culture system for respiratory research, we developed the PneumaCult™ Alveolar Organoid Expansion and Differentiation Media for the highly efficient expansion of isolated primary human AT2 cells and subsequent differentiation into AT1 cells. Alveolar organoids were established from a panel of various donors (n=5) by culturing purified human AT2 cells in Corning® Matrigel® domes with serum-free PneumaCult™ Alveolar Organoid Expansion Medium. Typically by day 10-14 the organoids are fully established and display a spherical morphology. Alveolar organoids can then be either expanded long-term by passaging cultures as single cells in Expansion Medium or differentiated into AT1 cells using the PneumaCult™ Alveolar Organoid Differentiation Medium. Organoids in PneumaCult™ Alveolar Organoid Expansion Medium contain self-renewing AT2 cells marked by the expression of HT2-280 in 89.9 +/- 14.5 (mean +/- SD;n=5 donors) of cells and the presence of Pro-SPC, demonstrate a great expansion potential of > 10,000-fold with more than 13 population doublings within 10 passages (n=5 donors). Alveolar organoids differentiated for 10 days in the PneumaCult™ Alveolar Organoid Differentiation Medium downregulate AT2 markers HT2-280 and Pro-SPC and start expressing AT1 markers HT1-56 in 93.8 +/- 7.2 (mean +/- SD;n=5 donors) of cells and are positive for RAGE and GPRC5a. Furthermore, we assessed the expression of SARS-CoV-2 entry receptor ACE2, which is present in both undifferentiated and differentiated alveolar organoids.To investigate the use of these alveolar organoids for infectious disease modeling, AT2-containing alveolar organoids were transduced with a GFP-labelled Respiratory Syncytial Virus (RSV). Alveolar organoids were susceptible to viral infection and replication was confirmed by fluorescence microscopy and quantitative PCR. In summary, the PneumaCult™ Alveolar Organoid Expansion and Differentiation Media are highly efficient and reproducible tools for the feeder-free expansion of AT2 cells and robust differentiation into AT1 cells, which can be used for infectious disease modeling.","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114654633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Li, T. Li, G. Kitsios, W. Bain, J. Lee, A. Morris, C. Zou
{"title":"Ubiquitin Proteasome Degradation Is Involved in the ProteinStability of SARS-CoV-2 Encoded Proteins","authors":"W. Li, T. Li, G. Kitsios, W. Bain, J. Lee, A. Morris, C. Zou","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3613","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3613","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130656569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Baker, P. Fenwick, C. Koss, H. Owles, K. E. El Kasmi, P. J. Barnes, L. Donnelly
{"title":"Inhibition of the IL-36 Receptor Reduces Viral Induced Cross-Talk Between Small Airway Epithelial Cells and Fibroblast in COPD","authors":"J. Baker, P. Fenwick, C. Koss, H. Owles, K. E. El Kasmi, P. J. Barnes, L. Donnelly","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3623","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3623","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127337391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Kato, T. Asakura, C. Edwards, H. Dang, Y. Mikami, K. Okuda, G. Chen, L. Sun, R. Gilmore, P. Hawkins, S. M. Hewitt, D. Chertow, NIH COVID-19 Autopsy Consortium, A. Borczuk, F. J. Martínez, L. Thorne, F. Askin, C. Ehre, S. Randell, W. O'Neal, R. Baric, R. C. Boucher
{"title":"Prevalence and Mechanisms of Bronchiolar Mucus Plugging in COVID-19 Lung Disease","authors":"T. Kato, T. Asakura, C. Edwards, H. Dang, Y. Mikami, K. Okuda, G. Chen, L. Sun, R. Gilmore, P. Hawkins, S. M. Hewitt, D. Chertow, NIH COVID-19 Autopsy Consortium, A. Borczuk, F. J. Martínez, L. Thorne, F. Askin, C. Ehre, S. Randell, W. O'Neal, R. Baric, R. C. Boucher","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3612","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3612","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"116 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123146939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Tsai, W. Osman, A. Elhance, James H. Adair, L. Chafin, J. Londino, R. Mallampalli
{"title":"FBXO45 Targets IFNLR1 to Impair IFN-lambda Signaling During Influenza Infection","authors":"M. Tsai, W. Osman, A. Elhance, James H. Adair, L. Chafin, J. Londino, R. Mallampalli","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3622","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3622","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123239158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. S. Hussain, E. F. Libby, J. Tipper, S. Phillips, Q. Li, J. Campos-Gómez, J.E. Peabody Lever, K. Harrod, S. Rowe
{"title":"SARS CoV-2 Infection Is Increased with Cigarette Smoke Exposure in Airway Epithelial Cells In Vitro and Blocked by Dual ACE2 and TMPRSS2 Blockade","authors":"S. S. Hussain, E. F. Libby, J. Tipper, S. Phillips, Q. Li, J. Campos-Gómez, J.E. Peabody Lever, K. Harrod, S. Rowe","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3615","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3615","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129133936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Okuda, K. H. Dinnon Iii, S. Leist, H. Dang, K. Gully, G. de la Cruz, M. Evangelista, T. Asakura, R. Gilmore, P. Hawkins, S. Nakano, A. West, A. Schaefer, Lisa E. Gralinski, M. Zweigart, S. Dong, J. Mcbride, M. R. Cooley, M. K. Love, M. Sakthivel, Y.Z. Lee, J. Hagood, J. Mock, W. O’Neal, S. Montgomery, R. C. Boucher, R. Baric
{"title":"Spatial Transcriptional Profiling of Chronic Pulmonary Disease in a Mouse-Adapted Model of SARS-CoV-2","authors":"K. Okuda, K. H. Dinnon Iii, S. Leist, H. Dang, K. Gully, G. de la Cruz, M. Evangelista, T. Asakura, R. Gilmore, P. Hawkins, S. Nakano, A. West, A. Schaefer, Lisa E. Gralinski, M. Zweigart, S. Dong, J. Mcbride, M. R. Cooley, M. K. Love, M. Sakthivel, Y.Z. Lee, J. Hagood, J. Mock, W. O’Neal, S. Montgomery, R. C. Boucher, R. Baric","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3621","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3621","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"156 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122069499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Barrero, V. Parmar, K. Taylor, F. Wang, M. Florez
{"title":"In Vitro Evaluation of Inhaled Drugs Therapies to Prevent Severe COVID19","authors":"C. Barrero, V. Parmar, K. Taylor, F. Wang, M. Florez","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3620","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3620","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115057486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Anathy, N. Chamberlain, M. Ruban, A. Kumar, Z. Mark, J. Alcorn, S. Bruno, A. Jegga, D. Souza de Lima
{"title":"Targeting Endoplasmic Reticulum (ER) Based Redox Regulation of Influenza and Host Proteins a Novel Avenue for Therapy","authors":"V. Anathy, N. Chamberlain, M. Ruban, A. Kumar, Z. Mark, J. Alcorn, S. Bruno, A. Jegga, D. Souza de Lima","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3608","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3608","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124941819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. S. Bednash, F. Johns, A. Elhance, James H. Adair, J. Londino
{"title":"Deubiquitinases Regulate ACE2 Protein Stability and SARS-CoV-2 Viral Infection in Epithelial Cells","authors":"J. S. Bednash, F. Johns, A. Elhance, James H. Adair, J. Londino","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3614","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3614","url":null,"abstract":"","PeriodicalId":277739,"journal":{"name":"B107. MOLECULAR MECHANISMS OF SARS-CoV-2, INFLUENZA, AND OTHER LUNG INFECTIONS","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122269467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}