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Series GSE82158 Query DataSets for GSE82158
Status Public on Jun 25, 2017
Title Ontogeny of alveolar macrophages is a critical determinant of function during lung fibrosis [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
Overall design Monocytes, interstitial macrophages, and alveolar macrophages separated by high or low expression of Siglec F were isolated from Casp8flox/flox at 14 and 19-21 days following bleomycin-induced fibrosis and Siglec F high alveolar macrophages were isolated from naïve mice. The same experiment was repeated for CD11cCreCasp8flox/flox and LysMCreCasp8flox/flox mice and was repeated without naïve mice for CD11cCreCasp8flox/floxRIPK3-/- and LysMCreCasp8flox/floxRIPK3-/- mice. Donor and recipient alveolar macrophages were isolated 10 months following bleomycin injury from bone marrow chimeras. Transcriptome analysis was performed. Experiments were performed with 2-5 replicates.
Contributor(s) Misharin AV, Budinger GS, Perlman HR, Reyfman PA, Anekalla KR, Marshall SA, Morgan VK
Citation(s) 28694385
Submission date Jun 02, 2016
Last update date May 15, 2019
Contact name Alexander Misharin
Organization name Northwestern University Feinberg School of Medicine
Department Medicine - Pulmonary
Street address 240 E Huron M-300
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (163)
GSM2184957 C8flx_IM_D14_1
GSM2184958 C8flx_IM_D14_2
GSM2184959 C8flx_IM_D14_3
BioProject PRJNA324226
SRA SRP076019

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Supplementary file Size Download File type/resource
GSE82158_macrophage_ontogeny_norm_counts.txt.gz 18.6 Mb (ftp)(http) TXT
GSE82158_shielded_chimera_norm_counts.txt.gz 974.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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