Inferring tumor subclonality
| العنوان: | Inferring tumor subclonality |
|---|---|
| المؤلفون: | Wes Sanders, Ralph S. Baric, Heather A. Vincent, Angela Wahl, Nathaniel J. Moorman, J. Victor Garcia, Erik M. Lenarcic, Allison Boone, Miriam Braunstein, Christian R. Aguilera-Sandoval, Yinyan Xu, Nilu Goonetilleke, Paul A. Dayton, William H. Hildebrand, Maria Abad Fernandez, Chandrav De, Adam S. Cockrell, Claire Johnson, Raymond J. Pickles, Nathaniel J. Schramm, Laura Rank, Isabel G. Newsome, Rachel A. Cleary |
| المصدر: | Nature Biotechnology Nature biotechnology |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Cytomegalovirus, Mice, SCID, Antibodies, Viral, Virus Replication, Applied Microbiology and Biotechnology, Biochemistry, Mice, 0302 clinical medicine, Neoplasms, Lung, Genetics, 0303 health sciences, Zika Virus Infection, Immunohistochemistry, 3. Good health, Haematopoiesis, medicine.anatomical_structure, Mutation (genetic algorithm), Middle East Respiratory Syndrome Coronavirus, Cytokines, Molecular Medicine, Female, Coronavirus Infections, Biotechnology, Biomedical Engineering, Antigen-Presenting Cells, Bioengineering, Biology, Tropism, Article, Virus, 03 medical and health sciences, In vivo, medicine, Animals, Humans, Antigen-presenting cell, Molecular Biology, 030304 developmental biology, Mesenchymal stem cell, Zika Virus, Cell Biology, Virology, Disease Models, Animal, Gene Expression Regulation, Mutation, Humanized mouse, Bone marrow, 030217 neurology & neurosurgery |
| الوصف: | A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics. |
| تدمد: | 1548-7105 1548-7091 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc55f8e20e208959483e150be43a478bTest https://doi.org/10.1038/s41592-020-0777-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc55f8e20e208959483e150be43a478b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15487105 15487091 |
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