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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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001312 |
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| Summary: | 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. |
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| ISSN: | 2589-0042 |