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| Status |
Public on Jun 21, 2019 |
| Title |
Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A comprehensive understanding of the changes in gene expression in cell types involved in idiopathic pulmonary fibrosis (IPF) will shed light on the mechanisms underlying the loss of alveolar epithelial cells, and development of honeycomb cysts and fibroblastic foci. We sought to understand changes in IPF lung cell transcriptomes and gain insight into innate immune aspects of pathogenesis. We investigated IPF pathogenesis using single cell RNA-sequencing of fresh lung explants, comparing human IPF fibrotic lower lobes reflecting late disease, upper lobes reflecting early disease and normal lungs. IPF lower lobes showed increased fibroblasts, and basal, ciliated, goblet and club cells, but decreased alveolar epithelial cells, and marked alterations in inflammatory cells. We found three discrete macrophage subpopulations in normal and fibrotic lungs, one expressing monocyte markers, one highly expressing FABP4 and INHBA (FABP4hi), and one highly expressing SPP1 and MERTK (SPP1hi). SPP1hi macrophages in fibrotic lower lobes showed highly upregulated SPP1 and MERTK expression. Low-level local proliferation of SPP1hi macrophages in normal lungs was strikingly increased in IPF lungs. Co-localization and causal modeling supported the role for these highly proliferative SPP1hi macrophages in activation of IPF myofibroblasts in lung fibrosis. These data suggest SPP1hi macrophages contribute importantly to lung fibrosis in IPF, and that therapeutic strategies targeting MERTK and macrophage proliferation may show promise for treatment of this disease.
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| Overall design |
Single cell RNA-Seq 3 Prime gene expression comparison of normal/healthy donor lung tissue with upper IPF lobe tissue and lower IPF lobe tissue. Single-cell suspensions from three normal control donor lungs and separate upper and lower sections of three lungs from patients with idiopathic pulmonary fibrosis were prepared. Single cell RNA-seq libraries were generated using 3' V2 chemistry kit on Chromium Single cell controller (10x Genomics). For analysis of normal lung composition and cell populations, three additional lungs were included (2 on V1 chemistry, 1 on V2 chemistry). Brochoalvelolar lavage (BAL) samples were both run on V2 chemistry. This GEO submission contains only processed data (raw counts in sparse matrix format).
***Please note that the GEO records contain only processed data (raw counts in sparse matrix format) as raw data is unavailable due to patient privacy concerns.
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| Contributor(s) |
Morse C, Tabib T, Sembrat J, Trejo Bittar HE, Buschur K, Valenzi E, Jiang Y, Kass D, Gibson K, Chen W, Mora A, Benos P, Rojas M, Lafyatis R |
| Citation(s) |
31221805, 37706427 |
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| Submission date |
Mar 07, 2019 |
| Last update date |
May 06, 2024 |
| Contact name |
Tracy Tabib |
| Organization name |
University of Pittsburgh
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| Department |
Department of Medicine
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| Lab |
Laboratory of Robert Lafyatis
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| Street address |
200 Lothrop Street
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15213 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA526088 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128033_RAW.tar |
589.1 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| Processed data provided as supplementary file |
| Raw data not provided for this record |
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