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This study integrated multiple daytime single\u2010cell RNA\u2010seq datasets from the pineal glands of zebrafish, rats, and monkeys, providing a detailed examination of the evolutionary transition at single\u2010cell resolution. We identified key factors responsible for the anatomical and functional transformation of the pineal gland. We retrieved and integrated daytime single\u2010cell transcriptomic datasets from the pineal glands of zebrafish, rats, and monkeys, resulting in a total of 22\u2009431 cells after rigorous quality filtering. Comparative analysis was then conducted to elucidate the evolution of pineal cells, their photosensitivity, their role in melatonin production, and the signaling processes within the glands of these species. Our analysis identified distinct cellular compositions of the pineal gland in zebrafish, rats, and monkeys. Zebrafish photoreceptors exhibited comprehensive phototransduction gene expression, while specific genes, including transducin (<jats:italic>Gngt1<\/jats:italic>, <jats:italic>Gnb3<\/jats:italic>, and <jats:italic>Gngt2<\/jats:italic>) and phosducin (<jats:italic>Pdc<\/jats:italic>), were consistently present in mammalian pinealocytes. We found transcriptional similarities between the pineal gland and retina, underscoring shared evolutionary and functional pathways. Zebrafish displayed unique light\u2010responsive circadian gene activity compared to rats and monkeys. Key ligand\u2010receptor interactions were identified, especially involving <jats:italic>MDK<\/jats:italic> and <jats:italic>PTN<\/jats:italic>, influencing melatonin synthesis across species. Furthermore, we observed species\u2010specific GPCR (G protein\u2010coupled receptors) expressions related to melatonin synthesis and their alignment with retinal expressions. Our findings also highlighted specific transcription factors (TFs) and regulatory networks associated with pineal gland evolution and function. Our study provides a detailed analysis of the pineal gland's evolution from fish to mammals. We identified key transcriptional changes and controls that highlight the gland's functional diversity. Notably, we found significant ligand\u2010receptor interactions influencing melatonin synthesis and demonstrated parallels between pineal and retinal expressions. These insights enhance our understanding of the pineal gland's role in phototransduction, melatonin production, and circadian rhythms in vertebrates.<\/jats:p>","DOI":"10.1111\/jpi.12927","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T07:17:34Z","timestamp":1701242254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cross\u2010species single\u2010cell landscape of vertebrate pineal gland"],"prefix":"10.1111","volume":"76","author":[{"given":"Jihong","family":"Zheng","sequence":"first","affiliation":[{"name":"Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Song","sequence":"additional","affiliation":[{"name":"Fundamental Research Center, Shanghai Yangzhi 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