biostudies-literatureUnknown615(7950)Gurtner AIn the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils-elusive granulocytes that are implicated in a plethora of human pathologies^1-5-are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPNature151-157https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977678biostudies-literatureActive eosinophils regulate host defence and immune responses in colitis.PMC9977678Slack EValenta TMoor AEKrebs PRaju DBach KVu VPNunez NGBecher BArnold ICGonzalez-Perez IBorrelli CCrepaz DHandler KGschwend JSchneider CGurtner ALafzi ABasler KAcar IEStirm KfalseActive eosinophils regulate host defence and immune responses in colitis.In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils-elusive granulocytes that are implicated in a plethora of human pathologies^1-5-are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISP2023-01-01T00:00:00Z2023 Mar2025-04-18T14:12:31.399Z2025-04-07T00:12:56.836ZS-EPMC99776783650910610.1038/s41586-022-05628-7