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| Status |
Public on Sep 12, 2024 |
| Title |
Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Visium] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Pulmonary fibrosis (PF) is a chronic, progressive condition that represents the end-stage of many interstitial lung diseases (ILDs). Single-cell transcriptomic studies have revealed disease-emergent epithelial, fibroblast, and macrophage cell types/states in PF lungs, but the spatial contexts wherein these cells contribute to disease pathogenesis has remained uncertain. Using image-based spatial transcriptomics to profile gene expression changes in-situ across 28 lung samples from control and PF lungs, we characterized the expression of 343 genes in over 1 million nuclei at subcellular resolution. Using both cell-based and cell-agnostic approaches, we observed a diversity of distinct molecularly-defined spatial niches in control and PF lungs. Overlaying these computationally-defined niches with disease-associated histopathologic features, we identified novel patterns of dysregulation in alveoli informed by spatial context. We computationally segmented individual air spaces and using cell composition, we ordered airspaces from homeostatic to most dysregulated. Using this ordering we identified a series of stepwise molecular changes associated with progressive distal lung remodeling. Together, these results advance our understanding of the molecular programs underlying progressive PF.
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| Overall design |
To characterize the cellular and molecular architecture of the lung across health and disease, we generated a spatial transcriptomics dataset measuring the expression of 343 genes across 28 3-5 mm lung tissue cores from 6 unaffected (31.6%) and 13 PF (68.42%) donors using the 10X Genomics Xenium platform. To capture the regional heterogeneity of PF, we sampled paired sets of cores from more (MF) and less (LF) fibrotic regions of 9 individuals and larger biopsies encompassing a diversity of architectures of 3 individuals. Of the 13 PF patients, most were diagnosed with IPF (n = 7, 53.8%). The majority of donors self-reported European ancestry (78.9%), and 8 (42.1%) reported current or prior tobacco use.
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| Contributor(s) |
Vannan A, Lyu R, Williams AL, Negretti NM, Mee ED, Hirsh J, Hirsh S, Nichols DS, Taylor CJ, Polosukhin VV, McCall AS, Gokey JJ, Shim H, Ware LB, Bacchetta MJ, Shaver CM, Blackwell TS, Sucre JM, Kropski JA, McCarthy DJ, Banovich NE |
| Citation missing |
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| Submission date |
Sep 11, 2024 |
| Last update date |
Sep 13, 2024 |
| Contact name |
Nicholas Banovich |
| E-mail(s) |
nbanovich@tgen.org
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| Phone |
602-343-8432
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| Organization name |
TGen - Translational Genomics Research Institute
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| Department |
Integrated Cancer Genomics
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| Lab |
Banovich Lab
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| Street address |
445 North Fifth Street
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| City |
Phoenix |
| State/province |
AZ |
| ZIP/Postal code |
85004 |
| Country |
USA |
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| Platforms (1) |
| GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
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| Samples (1) |
| GSM8509590 |
IPFTMA5, Post-Xenium Visium HD (VUILD49LA, TILD113LA, TILD111LA, VUHD049) |
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| This SubSeries is part of SuperSeries: |
| GSE276945 |
Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis |
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| Relations |
| BioProject |
PRJNA1160022 |
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