Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution
Abstract Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (ME...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55325-4 |
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| author | Brianna R. Watson Biplab Paul Raza Ur Rahman Liat Amir-Zilberstein Åsa Segerstolpe Eliana T. Epstein Shane Murphy Ludwig Geistlinger Tyrone Lee Angela Shih Jacques Deguine Ramnik J. Xavier Jeffrey R. Moffitt Alan C. Mullen |
| author_facet | Brianna R. Watson Biplab Paul Raza Ur Rahman Liat Amir-Zilberstein Åsa Segerstolpe Eliana T. Epstein Shane Murphy Ludwig Geistlinger Tyrone Lee Angela Shih Jacques Deguine Ramnik J. Xavier Jeffrey R. Moffitt Alan C. Mullen |
| author_sort | Brianna R. Watson |
| collection | DOAJ |
| description | Abstract Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions. Finally, MERFISH and snRNA-seq analysis of fibrotic liver samples identify two hepatocyte populations that expand with injury and do not have clear zonal distributions. Together these spatial maps of the healthy and fibrotic liver provide a deeper understanding of the cellular and spatial remodeling that drives disease which, in turn, could provide new avenues for intervention and further study. |
| format | Article |
| id | doaj-art-7929901e00ce4dfaa2a4ea15937666cb |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7929901e00ce4dfaa2a4ea15937666cb2025-01-05T12:37:37ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-024-55325-4Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolutionBrianna R. Watson0Biplab Paul1Raza Ur Rahman2Liat Amir-Zilberstein3Åsa Segerstolpe4Eliana T. Epstein5Shane Murphy6Ludwig Geistlinger7Tyrone Lee8Angela Shih9Jacques Deguine10Ramnik J. Xavier11Jeffrey R. Moffitt12Alan C. Mullen13Program in Cellular and Molecular Medicine, Boston Children’s HospitalDivision of Gastroenterology, University of Massachusetts Chan Medical SchoolDivision of Gastroenterology, University of Massachusetts Chan Medical SchoolBroad Institute of Harvard and MITBroad Institute of Harvard and MITMassachusetts General HospitalBroad Institute of Harvard and MITCore for Computational Biomedicine, Department for Biomedical Informatics, Blavatnik Institute, Harvard Medical SchoolCore for Computational Biomedicine, Department for Biomedical Informatics, Blavatnik Institute, Harvard Medical SchoolMassachusetts General HospitalBroad Institute of Harvard and MITBroad Institute of Harvard and MITProgram in Cellular and Molecular Medicine, Boston Children’s HospitalDivision of Gastroenterology, University of Massachusetts Chan Medical SchoolAbstract Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions. Finally, MERFISH and snRNA-seq analysis of fibrotic liver samples identify two hepatocyte populations that expand with injury and do not have clear zonal distributions. Together these spatial maps of the healthy and fibrotic liver provide a deeper understanding of the cellular and spatial remodeling that drives disease which, in turn, could provide new avenues for intervention and further study.https://doi.org/10.1038/s41467-024-55325-4 |
| spellingShingle | Brianna R. Watson Biplab Paul Raza Ur Rahman Liat Amir-Zilberstein Åsa Segerstolpe Eliana T. Epstein Shane Murphy Ludwig Geistlinger Tyrone Lee Angela Shih Jacques Deguine Ramnik J. Xavier Jeffrey R. Moffitt Alan C. Mullen Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution Nature Communications |
| title | Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution |
| title_full | Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution |
| title_fullStr | Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution |
| title_full_unstemmed | Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution |
| title_short | Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution |
| title_sort | spatial transcriptomics of healthy and fibrotic human liver at single cell resolution |
| url | https://doi.org/10.1038/s41467-024-55325-4 |
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