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Hansen JN, Sun H, Kahnert K, Westenius E, Johannesson A, Villegas C, Le T, Tzavlaki K, Winsnes C, Pohjanen E, Mäkiniemi A, Fall J, Ballllosera Navarro F, Bäckström A, Lindskog C, Johansson F, von Feilitzen K, Delgado-Vega AM, Martinez Casals A, Mahdessian D, Uhlén M, Sheu SH, Lindstrand A, Axelsson U, Lundberg E
Cell - (-) - [2025-09-25; online 2025-09-25]
Primary cilia are critical organelles found on most human cells. Their dysfunction is linked to hereditary ciliopathies with a wide phenotypic spectrum. Despite their significance, the specific roles of cilia in different cell types remain poorly understood due to limitations in analyzing ciliary protein composition. We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. Our analysis identified the subciliary locations of 715 proteins across three cell lines, examining 128,156 individual cilia. We found that 69% of the ciliary proteome is cell-type specific, and 78% exhibited single-cilia heterogeneity. Our findings portray cilia as sensors tuning their proteome to effectively sense the environment and compute cellular responses. We reveal 91 cilia proteins and found a genetic candidate variant in CREB3 in one clinical case with features overlapping ciliopathy phenotypes. This open, spatial cilia atlas advances research on cilia and ciliopathies.
Clinical Genomics Stockholm [Service]
PubMed 41005307
DOI 10.1016/j.cell.2025.08.039
Crossref 10.1016/j.cell.2025.08.039
pii: S0092-8674(25)01029-3