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Spatially resolved deconvolution of the fibrotic niche in lung fibrosis
A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We ide...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073410/ https://www.ncbi.nlm.nih.gov/pubmed/35977489 http://dx.doi.org/10.1016/j.celrep.2022.111230 |
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author | Eyres, Michael Bell, Joseph A. Davies, Elizabeth R. Fabre, Aurelie Alzetani, Aiman Jogai, Sanjay Marshall, Ben G. Johnston, David A. Xu, Zijian Fletcher, Sophie V. Wang, Yihua Marshall, Gayle Davies, Donna E. Offer, Emily Jones, Mark G. |
author_facet | Eyres, Michael Bell, Joseph A. Davies, Elizabeth R. Fabre, Aurelie Alzetani, Aiman Jogai, Sanjay Marshall, Ben G. Johnston, David A. Xu, Zijian Fletcher, Sophie V. Wang, Yihua Marshall, Gayle Davies, Donna E. Offer, Emily Jones, Mark G. |
author_sort | Eyres, Michael |
collection | PubMed |
description | A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFβ/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis. |
format | Online Article Text |
id | pubmed-10073410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-100734102023-04-06 Spatially resolved deconvolution of the fibrotic niche in lung fibrosis Eyres, Michael Bell, Joseph A. Davies, Elizabeth R. Fabre, Aurelie Alzetani, Aiman Jogai, Sanjay Marshall, Ben G. Johnston, David A. Xu, Zijian Fletcher, Sophie V. Wang, Yihua Marshall, Gayle Davies, Donna E. Offer, Emily Jones, Mark G. Cell Rep Resource A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFβ/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis. Cell Press 2022-08-16 /pmc/articles/PMC10073410/ /pubmed/35977489 http://dx.doi.org/10.1016/j.celrep.2022.111230 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Resource Eyres, Michael Bell, Joseph A. Davies, Elizabeth R. Fabre, Aurelie Alzetani, Aiman Jogai, Sanjay Marshall, Ben G. Johnston, David A. Xu, Zijian Fletcher, Sophie V. Wang, Yihua Marshall, Gayle Davies, Donna E. Offer, Emily Jones, Mark G. Spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
title | Spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
title_full | Spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
title_fullStr | Spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
title_full_unstemmed | Spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
title_short | Spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
title_sort | spatially resolved deconvolution of the fibrotic niche in lung fibrosis |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073410/ https://www.ncbi.nlm.nih.gov/pubmed/35977489 http://dx.doi.org/10.1016/j.celrep.2022.111230 |
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