Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation
Summary: We have developed a single-cell assay that combines Cell Painting—a morphological profiling assay—with trajectory inference analysis. We have applied this morphological trajectory inference to the bi-potent HepaRG liver progenitor cell line allowing us to track liver cell fate and map small...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001312 |
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| author | Rebecca E. Graham Runshi Zheng Jesko Wagner Asier Unciti-Broceta David C. Hay Stuart J. Forbes Victoria L. Gadd Neil O. Carragher |
| author_facet | Rebecca E. Graham Runshi Zheng Jesko Wagner Asier Unciti-Broceta David C. Hay Stuart J. Forbes Victoria L. Gadd Neil O. Carragher |
| author_sort | Rebecca E. Graham |
| collection | DOAJ |
| description | Summary: We have developed a single-cell assay that combines Cell Painting—a morphological profiling assay—with trajectory inference analysis. We have applied this morphological trajectory inference to the bi-potent HepaRG liver progenitor cell line allowing us to track liver cell fate and map small-molecule-induced changes using a morphological atlas of liver cell differentiation. Our overarching goal is to demonstrate the potential of Cell Painting to study biological processes as continuous trajectories at the single-cell level, enhancing resolution and biological understanding. This work has identified small-molecule Src family kinase inhibitors that promote the differentiation of HepaRG cells toward a hepatocyte-like lineage as well as primary human hepatic progenitor cells toward a hepatocyte-like phenotype in vitro. These findings could significantly advance research on liver cell regeneration mechanisms and facilitate the development of cell-based and small-molecule therapies. |
| format | Article |
| id | doaj-art-080f78114bf6441ab9b014e875eefa34 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-080f78114bf6441ab9b014e875eefa342025-02-07T04:48:04ZengElsevieriScience2589-00422025-02-01282111871Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiationRebecca E. Graham0Runshi Zheng1Jesko Wagner2Asier Unciti-Broceta3David C. Hay4Stuart J. Forbes5Victoria L. Gadd6Neil O. Carragher7Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; Corresponding authorCentre for Regenerative Medicine, Institute of Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UKMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UKEdinburgh Cancer Research, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK; Cancer Research UK Scotland Centre, Edinburgh EH4 2XU, UKCentre for Regenerative Medicine, Institute of Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UKCentre for Regenerative Medicine, Institute of Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UKCentre for Regenerative Medicine, Institute of Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UKEdinburgh Cancer Research, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK; Cancer Research UK Scotland Centre, Edinburgh EH4 2XU, UK; Corresponding authorSummary: We have developed a single-cell assay that combines Cell Painting—a morphological profiling assay—with trajectory inference analysis. We have applied this morphological trajectory inference to the bi-potent HepaRG liver progenitor cell line allowing us to track liver cell fate and map small-molecule-induced changes using a morphological atlas of liver cell differentiation. Our overarching goal is to demonstrate the potential of Cell Painting to study biological processes as continuous trajectories at the single-cell level, enhancing resolution and biological understanding. This work has identified small-molecule Src family kinase inhibitors that promote the differentiation of HepaRG cells toward a hepatocyte-like lineage as well as primary human hepatic progenitor cells toward a hepatocyte-like phenotype in vitro. These findings could significantly advance research on liver cell regeneration mechanisms and facilitate the development of cell-based and small-molecule therapies.http://www.sciencedirect.com/science/article/pii/S2589004225001312Screening in health technologyBiological sciencesBiological sciences research methodologies |
| spellingShingle | Rebecca E. Graham Runshi Zheng Jesko Wagner Asier Unciti-Broceta David C. Hay Stuart J. Forbes Victoria L. Gadd Neil O. Carragher Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation iScience Screening in health technology Biological sciences Biological sciences research methodologies |
| title | Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation |
| title_full | Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation |
| title_fullStr | Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation |
| title_full_unstemmed | Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation |
| title_short | Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation |
| title_sort | single cell morphological tracking of cell states to identify small molecule modulators of liver differentiation |
| topic | Screening in health technology Biological sciences Biological sciences research methodologies |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001312 |
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