Prediction of Cell States and Key Transcription Factors of the Human Cornea Through Integrated Single-Cell Omics Analyses

    July 2025 in “ PNAS Nexus
    J.A. Arts, Sofia Fallo, Melanie S. Florencio, Jos G.A. Smits, Dulce Lima Cunha, Janou A. Y. Roubroeks, Mor M. Dickman, Vanessa L.S. LaPointe, Rosemary Yu, Huiqing Zhou
    TLDR A new tool accurately identifies human cornea cell states and key factors.
    This study integrates single-cell RNA sequencing data from four studies to create a comprehensive meta-atlas of human corneal cell states, identifying 21 distinct cell states, including novel markers and rare cell types like nonmyelinating corneal Schwann cells. A machine learning tool, cPredictor, was developed to accurately annotate these cell states, achieving a high weighted F1 score of 95.75% in cross-validation. The study also identifies key transcription factors, such as TP63, FOSL2, and PAX6, crucial for corneal cell state determination. The findings highlight differences between iPSC-derived corneal organoids and adult corneas, suggesting the need for improved maturation techniques. This work provides a robust reference for future research in corneal development, disease, and regeneration.
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