The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging
Open accessAbstract
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.
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Cites
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30566-3 · Cited by 27,263
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055
Geometric Control of Cell Life and Death
Chen, C. S., Mrksich, M., Huang, S., Whitesides, G. M., & Ingber, D. E. (1997) · Science · doi:10.1126/science.276.5317.1425 · Cited by 4,710
Self-citationGOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
Self-citationDNA methylation-based biomarkers and the epigenetic clock theory of ageing
Horvath, S., & Raj, K. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0004-3 · Cited by 3,095
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 2,842 · cited 1×
“One cluster (cluster 2) was characterized by increased expression of Lyz1 (Supplemental Figure 1F) and has been noted in previous data sets (15, 16).”
ResultTrained immunity: A program of innate immune memory in health and– disease
Netea, M. G., Joosten, L. A. B., Latz, E., Mills, K. H. G., Natoli, G., Stunnenberg, H. G., O’Neill, L. A. J., & Xavier, R. J. (2016) · Science · doi:10.1126/science.aaf1098 · Cited by 2,768
Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults
Jain, S., Self, W. H., Wunderink, R. G., Fakhran, S., Balk, R., Bramley, A. M., Reed, C., Grijalva, C. G., Anderson, E. J., Courtney, D. M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500245 · Cited by 2,323
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Metadata
- Authors
- McQuattie-Pimentel, A. C., Ren, Z., Joshi, N., Watanabe, S., Stoeger, T., Chi, M., Lu, Z., Sichizya, L., Aillon, R. P., Chen, C.-I., Soberanes, S., Chen, Z., Reyfman, P. A., Walter, J. M., Anekalla, K. R., Davis, J. M., Helmin, K. A., Runyan, C. E., Abdala-Valencia, H., Nam, K., Meliton, A. Y., Winter, D. R., Morimoto, R. I., Mutlu, G. M., Bharat, A., Perlman, H., Gottardi, C. J., Ridge, K. M., Chandel, N. S., Sznajder, J. I., Balch, W. E., Singer, B. D., Misharin, A. V., & Budinger, G. R. S.
- Affiliations
- Northwestern University (US)
- University of Chicago Medical Center (US)
- Scripps Research Institute (US)
- ORCID
- Ren, Ziyou
- Joshi, Nikita
- Watanabe, Satoshi
- Stoeger, Thomas
- Lu, Ziyan
- Sichizya, Lango
- Chen, Ching-I
- Soberanes, Saul
- Chen, Zhangying
- Reyfman, Paul A.
- Walter, James M.
- Anekalla, Kishore R.
- Helmin, Kathryn A.
- Runyan, Constance E.
- Abdala-Valencia, Hiam
- Winter, Deborah R.
- Morimoto, Richard I.
- Mutlu, Gökhan M.
- Bharat, Ankit
- Perlman, Harris
- Gottardi, Cara J.
- Ridge, Karen M.
- Chandel, Navdeep S.
- Sznajder, Jacob I.
- Balch, William E.
- Singer, Benjamin D.
- Misharin, Alexander V.
- Budinger, G.R. Scott
- Venue
- Journal of Clinical Investigation
- Published
- 2021-02-15
- Volume
- 131
- Issue
- 4
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC7919859
- OpenAlex
- W3133294399
- Cited by
- 177
- References
- 56
- Citations by year
- 2026: 30 · 2025: 35 · 2024: 31 · 2023: 30 · 2022: 34 · 2021: 17
- FWCI
- 10.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (AG490665, HL135124,AG049665,AI135964, HL071643,HL14575)
- Veterans Administration (CX01777)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- alveolar macrophages, lung aging, lung microenvironment, extracellular matrix, hyaluronic acid, macrophage proliferation, influenza A virus infection, GM-CSF signaling, bone marrow-derived macrophages, lineage tracing, parabiosis, single-cell transcriptomics
- MeSH terms
- RNA-Seq, Aging, Animals, Humans, Lung, Mice, Transgenic, Macrophages, Alveolar, Mice, Cellular Microenvironment
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