Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation. Graham et al.
Description
Dataset published by Graham et al. 2024 which contains HepaRG Cell Painting features. Cell Painting screen using the liver progenitor cell line HepaRG which undergoes bilineage differentiation to produce hepatocyte-like and biliary-like cells. We performed a chemical screen to find small-molecules that promoted differentiation of the cells using the Cell Painting morphological features. The screen was performed using the median image level data (agg_screen_data). We then leveraged the single cell data to determine whether the hit compounds affected the proportions of hepatocyte-like and cholangiocyte-like cells. To do this we images the cells over the course of 4 weeks while they differentiated to generate a morphological atlas of HepaRG differentiation and then we overlaid the single cell drug treated cells. We used trajectory inference to quantify any changes. We found that SRK family kinase inhibitors led to an almost pure cell population of hepatocyte-like cells. File Description Aggregated_screen_data_fig1_fig2 contains: Primary_screen_aggregated_data.csv : primary screen image median aggregated data. Val_01_agg_formatted.csv : validation dose response (rep 1) image median aggregated data. Val_02_agg_formatted.csv : validation dose response (rep 2) image median aggregated data. Val_03_agg_formatted.csv : validation dose response (rep 3) image median aggregated data. Sc_raw_subsampled_timecourse_data.csv : raw single cell downsampled timecourse data of HepaRG differentiation Sc_raw_subsampled_dose_response_data.csv : raw single cell downsampled dose response validation data Sc_cleaned_raw_features_timecourse_and_dose_responses_combined.csv : final cleaned dataset used in paper. Biological thresholds applied, doublets removed, and remaining extreme outlier cluster removed. Raw feature values (pre- standardisation). liver_pseudotime_cp_eddie.cppipe contains the CellProfiler pipeline used to generate the morphological features at the single cell level.