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| Status |
Public on Sep 16, 2024 |
| Title |
Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade [Ipt] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Recently, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2 has been described in several models of organ injury and cancer, and linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, given systemically or locally, leads to an increase in this putative pro-fibrotic macrophage in the lung and that this macrophage state can only be adopted by monocytically derived cells and not resident alveolar macrophages. Unexpectedly, using a bleomycin and COVID19 model of lung injury and fibrosis, we find that the expansion of these macrophages before lung injury does not promote fibrosis but rather appears to ameliorate it. This suggests that these damage-associated macrophages are not by themselves drivers of fibrosis in the lung.
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| Overall design |
CD45.1 Csf2raKO mice were transplanted with CD45.2 WT alveolar macrophages. aNotch2 or control antibody was applied IT to the mice. Lung intersitital macrophages, monocytes, and alveolar machrophages were isolated, labeled with CD45.1 and CD45.2 CITE-Seq antibodies and analyzed using the 10x system (5').
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| Contributor(s) |
Cruz Tleugabulova M, Melo S, Lechner A, Corak B, Schneider C, Nitschke M, Shaw A |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 16, 2024 |
| Last update date |
Sep 16, 2024 |
| Contact name |
Sandra Melo |
| Organization name |
Genentech, Inc.
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| Street address |
1 DNA Way
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| City |
South San Francisco |
| ZIP/Postal code |
94080 |
| Country |
USA |
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| Platforms (1) |
| GPL34290 |
Illumina NovaSeq X Plus (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1161684 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE277297_IPt.h5ad |
1.4 Gb |
(ftp)(http) |
H5AD |
| GSE277297_feature_reference_AMT.csv.gz |
500 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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