{"entity": "publication", "iuid": "72ac7b591a3d43b18c8d9b09a6b47006", "timestamp": "2026-10-23T17:33:29.333Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/72ac7b591a3d43b18c8d9b09a6b47006.json"}, "display": {"href": "https://publications.scilifelab.se/publication/72ac7b591a3d43b18c8d9b09a6b47006"}}, "title": "High-content morphological profiling by Cell Painting in 3D spheroids.", "authors": [{"family": "Ringers", "given": "Christa", "initials": "C", "orcid": "0000-0002-0807-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/1870bfae83214898acf048b2ecbd81ba.json"}}, {"family": "Holmberg", "given": "David", "initials": "D"}, {"family": "Larsson", "given": "Anders", "initials": "A"}, {"family": "Jung", "given": "Bomi", "initials": "B"}, {"family": "Jarvius", "given": "Malin", "initials": "M", "orcid": "0000-0002-1565-6155", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6b510afc21748adb6b432173c3fdab2.json"}}, {"family": "Luchniak", "given": "Anna", "initials": "A"}, {"family": "Ros\u00e9n", "given": "Dan", "initials": "D"}, {"family": "Johansson", "given": "Martin", "initials": "M"}, {"family": "Georgiev", "given": "Polina", "initials": "P"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Flobak", "given": "\u00c5smund", "initials": "\u00c5", "orcid": "0000-0002-3357-425X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3dbad688aeb44d039f3bc7e51f75b2bf.json"}}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "Spjuth", "given": "Ola", "initials": "O", "orcid": "0000-0002-8083-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/605dbd52684d4e54ae4150a9933abe6e.json"}}], "type": "journal article", "published": "2026-10-21", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "issn-l": "2041-1723"}, "abstract": "Cell Painting is a popular high-content imaging assay that captures the shape and internal organization of 2D cell cultures at scale. While 3D cell cultures are more physiologically relevant models - especially for studying drug perturbations - they remain challenging to image because light scatters before it reaches the cultures' interior. Here, we introduce a scalable method to adapt Cell Painting for 3D spheroids. We show that tissue-clearing, a technique that makes spheroids transparent, combined with a focusing routine that locates spheroids on the fly, enables Cell Painting at single-cell level inside intact spheroids. By profiling 52 clinically relevant drugs, we show that single-cell fingerprints clustered by biological pathway and resolved drug effects more robustly than those of flattened spheroid-wide views. Notably, the effect of two drugs, 5-fluorouracil and olaparib, nearly indistinguishable in 2D monolayers, diverged in spheroids. This finding was then corroborated by DNA-damage, cell-cycle, and gene-expression assays. The workflow runs on a spinning-disk confocal microscope in a standard 384-well plate format, making single-cell 3D profiling accessible to laboratories already performing Cell Painting.", "doi": "10.1038/s41467-026-78596-5", "pmid": "42907469", "labels": {"Chemical Biology Consortium Sweden": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-026-78596-5"}], "notes": [], "created": "2026-10-23T10:25:21.254Z", "modified": "2026-10-23T10:25:21.310Z"}