Cargando…
Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis
Liver fibrosis and cirrhosis have limited therapeutic options and represent a serious unmet patient need. Recent use of single‐cell RNA sequencing (scRNAseq) has identified enriched cell types infiltrating cirrhotic livers but without defining the microanatomical location of these lineages thoroughl...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426406/ https://www.ncbi.nlm.nih.gov/pubmed/35726350 http://dx.doi.org/10.1002/hep4.2001 |
_version_ | 1784778672221192192 |
---|---|
author | Chung, Brian K. Øgaard, Jonas Reims, Henrik Mikael Karlsen, Tom H. Melum, Espen |
author_facet | Chung, Brian K. Øgaard, Jonas Reims, Henrik Mikael Karlsen, Tom H. Melum, Espen |
author_sort | Chung, Brian K. |
collection | PubMed |
description | Liver fibrosis and cirrhosis have limited therapeutic options and represent a serious unmet patient need. Recent use of single‐cell RNA sequencing (scRNAseq) has identified enriched cell types infiltrating cirrhotic livers but without defining the microanatomical location of these lineages thoroughly. To assess whether fibrotic liver regions specifically harbor enriched cell types, we explored whether whole‐tissue spatial transcriptomics combined with scRNAseq and gene deconvolution analysis could be used to localize cell types in cirrhotic explants of patients with end‐stage liver disease (total n = 8; primary sclerosing cholangitis, n = 4; primary biliary cholangitis, n = 2, alcohol‐related liver disease, n = 2). Spatial transcriptomics clearly identified tissue areas of distinct gene expression that strongly correlated with the total area (Spearman r = 0.97, p = 0.0004) and precise location (parenchyma, 87.9% mean congruency; range, 73.1%–97.1%; fibrosis, 68.5% mean congruency; range, 41.0%–91.7%) of liver regions classified as parenchymal or fibrotic by conventional histology. Deconvolution and enumeration of parenchymal and fibrotic gene content as measured by spatial transcriptomics into distinct cell states revealed significantly higher frequencies of ACTA2+ FABP4+ and COL3A1+ mesenchymal cells, IL17RA+ S100A8+ and FCER1G+ tissue monocytes, VCAM1+ SDC3+ Kupffer cells, CCL4+ CCL5+ KLRB1+ and GZMA+ IL17RA+ T cells and HLA‐DR+, CD37+ CXCR4+ and IGHM+ IGHG+ B cells in fibrotic liver regions compared with parenchymal areas of cirrhotic explants. Conclusion: Our findings indicate that spatial transcriptomes of parenchymal and fibrotic liver regions express unique gene content within cirrhotic liver and demonstrate proof of concept that spatial transcriptomes combined with additional RNA sequencing methodologies can refine the localization of gene content and cell lineages in the search for antifibrotic targets. |
format | Online Article Text |
id | pubmed-9426406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94264062022-08-31 Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis Chung, Brian K. Øgaard, Jonas Reims, Henrik Mikael Karlsen, Tom H. Melum, Espen Hepatol Commun Original Articles Liver fibrosis and cirrhosis have limited therapeutic options and represent a serious unmet patient need. Recent use of single‐cell RNA sequencing (scRNAseq) has identified enriched cell types infiltrating cirrhotic livers but without defining the microanatomical location of these lineages thoroughly. To assess whether fibrotic liver regions specifically harbor enriched cell types, we explored whether whole‐tissue spatial transcriptomics combined with scRNAseq and gene deconvolution analysis could be used to localize cell types in cirrhotic explants of patients with end‐stage liver disease (total n = 8; primary sclerosing cholangitis, n = 4; primary biliary cholangitis, n = 2, alcohol‐related liver disease, n = 2). Spatial transcriptomics clearly identified tissue areas of distinct gene expression that strongly correlated with the total area (Spearman r = 0.97, p = 0.0004) and precise location (parenchyma, 87.9% mean congruency; range, 73.1%–97.1%; fibrosis, 68.5% mean congruency; range, 41.0%–91.7%) of liver regions classified as parenchymal or fibrotic by conventional histology. Deconvolution and enumeration of parenchymal and fibrotic gene content as measured by spatial transcriptomics into distinct cell states revealed significantly higher frequencies of ACTA2+ FABP4+ and COL3A1+ mesenchymal cells, IL17RA+ S100A8+ and FCER1G+ tissue monocytes, VCAM1+ SDC3+ Kupffer cells, CCL4+ CCL5+ KLRB1+ and GZMA+ IL17RA+ T cells and HLA‐DR+, CD37+ CXCR4+ and IGHM+ IGHG+ B cells in fibrotic liver regions compared with parenchymal areas of cirrhotic explants. Conclusion: Our findings indicate that spatial transcriptomes of parenchymal and fibrotic liver regions express unique gene content within cirrhotic liver and demonstrate proof of concept that spatial transcriptomes combined with additional RNA sequencing methodologies can refine the localization of gene content and cell lineages in the search for antifibrotic targets. John Wiley and Sons Inc. 2022-06-20 /pmc/articles/PMC9426406/ /pubmed/35726350 http://dx.doi.org/10.1002/hep4.2001 Text en © 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Chung, Brian K. Øgaard, Jonas Reims, Henrik Mikael Karlsen, Tom H. Melum, Espen Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
title | Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
title_full | Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
title_fullStr | Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
title_full_unstemmed | Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
title_short | Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
title_sort | spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426406/ https://www.ncbi.nlm.nih.gov/pubmed/35726350 http://dx.doi.org/10.1002/hep4.2001 |
work_keys_str_mv | AT chungbriank spatialtranscriptomicsidentifiesenrichedgeneexpressionandcelltypesinhumanliverfibrosis AT øgaardjonas spatialtranscriptomicsidentifiesenrichedgeneexpressionandcelltypesinhumanliverfibrosis AT reimshenrikmikael spatialtranscriptomicsidentifiesenrichedgeneexpressionandcelltypesinhumanliverfibrosis AT karlsentomh spatialtranscriptomicsidentifiesenrichedgeneexpressionandcelltypesinhumanliverfibrosis AT melumespen spatialtranscriptomicsidentifiesenrichedgeneexpressionandcelltypesinhumanliverfibrosis |