Consensus Pituitary Atlas, a scalable resource for annotation, novel marker discovery and analyses in pituitary gland research

Köver, B.; Willis, T. L.; Sherwin, O.; Kaufman-Cook, J.; Kemkem, Y.; Vazquez Segoviano, M.; Lodge, E. J.; Zamojski, M.; Mendelev, N.; Zhang, Z.; Smith, G. R.; Bernard, D. J.; Lu, H.-C.; Sealfon, S. C.; Ruf-Zamojski, F.; Andoniadou, C. L.

doi:10.1101/2025.10.28.685060

bioRxiv · 10.1101/2025.10.28.685060

Consensus Pituitary Atlas, a scalable resource for annotation, novel marker discovery and analyses in pituitary gland research

Köver, B.·Willis, T. L.·Sherwin, O.·Kaufman-Cook, J.·Kemkem, Y.·Vazquez Segoviano, M.·Lodge, E. J.·Zamojski, M.·Mendelev, N.·Zhang, Z.·Smith, G. R.·Bernard, D. J.·Lu, H.-C.·Sealfon, S. C.·Ruf-Zamojski, F.·Andoniadou, C. L.

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Abstract

Previous single-cell profiling studies of the pituitary gland have yielded minimally reproducible insights largely due to their low statistical power and methodological inconsistencies. To address this problem, we generated a uniformly pre-processed Consensus Pituitary Atlas (CPA) using all existing mouse pituitary single-cell datasets (267 biological replicates, >1.1 million high-quality cells). The CPA revealed novel cell typing and lineage markers, including low-expression transcripts that previous analyses could not detect. The scale of the CPA enabled the development of machine learning models to automate and standardize cell type annotation and doublet identification for future studies. Leveraging the curated metadata, we identified sex-biased and age-dependent gene expression patterns at cell type resolution. To identify drivers of cell fates, first we determined consensus cell communication patterns. Secondly, we used RNA-sequencing and chromatin accessibility data to identify transcription factors associated with cell fates across modalities. The epitome platform acts as an interface with the CPA, allowing streamlined user-friendly analyses. HighlightsO_LIUniform processing of 267 mouse pituitary single-cell datasets (>1.1M cells) C_LIO_LIThe statistical power enabled cell type, sex- and age-specific marker discovery C_LIO_LIMachine learning models facilitate doublet detection and cell typing in new datasets C_LIO_LIepitome platform provides programming-free data access and visualizations C_LI

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Köver, B., Willis, T. L., Sherwin, O., Kaufman-Cook, J., Kemkem, Y., Vazquez Segoviano, M., Lodge, E. J., Zamojski, M., Mendelev, N., Zhang, Z., Smith, G. R., Bernard, D. J., Lu, H.-C., Sealfon, S. C., Ruf-Zamojski, F., Andoniadou, C. L.. 2025-10-29. Consensus Pituitary Atlas, a scalable resource for annotation, novel marker discovery and analyses in pituitary gland research. https://doi.org/10.1101/2025.10.28.685060

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