{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:16Z","timestamp":1785411376534,"version":"3.56.0"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"the Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["Grant No. 2023ZD0506800"],"award-info":[{"award-number":["Grant No. 2023ZD0506800"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant Nos. 32271165"],"award-info":[{"award-number":["Grant Nos. 32271165"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,12]]},"abstract":"<jats:p>\n                    The mammalian pineal gland maintains normal circadian rhythms and homeostasis by secreting melatonin. However, the lack of a single-cell-resolved regulatory map limits our understanding of how these neuroendocrine functions are orchestrated. Here, we constructed a multiomics atlas of the pineal gland from\n                    <jats:italic toggle=\"yes\">Macaca fascicularis<\/jats:italic>\n                    by integrating snRNA-seq, snATAC-seq, and spatial transcriptomics. We identified pinealocytes as the predominant cell type, alongside six glial and vascular lineages. Chromatin accessibility analysis delineated cell-type-specific regions enriched for melatonin synthesis and phototransduction genes. Notably, we resolved a dual-layer regulatory architecture: While melatonin synthesis programs are robustly organized, circadian clock regulators exhibit a distinct, sparse spatial pattern. Coexpression networks further identified core modules and regulatory hubs\u2014including CRX\/OTX2, LHX4, and RORA\u2014that integrate these circadian and light-responsive signals. Cell-cell communication analysis identified signaling axes, such as\n                    <jats:italic toggle=\"yes\">PTN<\/jats:italic>\n                    -\n                    <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">SDC2<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">RA<\/jats:italic>\n                    -\n                    <jats:italic toggle=\"yes\">RORB<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                    -\n                    <jats:italic toggle=\"yes\">ERBB4<\/jats:italic>\n                    , that potentially coordinate this spatial functional organization. Integrating genetic traits showed that sleep and neuropsychiatric risk variants preferentially map to these pineal regulatory modules. Specifically, sleep-associated loci converged on\n                    <jats:italic toggle=\"yes\">MEIS1<\/jats:italic>\n                    -linked elements, while bipolar disorder-associated loci highlighted candidate genes of\n                    <jats:italic toggle=\"yes\">RDH12<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">SDK2<\/jats:italic>\n                    . Overall, this study reveals the cellular diversity and spatial regulatory logic of the primate pineal gland, providing a physiological foundation for investigating circadian and neuroendocrine regulation in healthy and disease models.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2524839123","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:15:31Z","timestamp":1777997731000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell multiomic and spatial landscape of the primate pineal gland reveals circadian and melatonin regulatory architecture"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0875-5447","authenticated-orcid":false,"given":"Jihong","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0262-9155","authenticated-orcid":false,"given":"Jianjun","family":"Lyu","sequence":"additional","affiliation":[{"name":"Hubei Topgene Xinsheng Biotechnology Co., Ltd, No. 41, Great Health Industrial Park, South of the Optics Valley, Jiangxia District, Wuhan","place":["Hubei Province, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqun","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05kvm7n82","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, School of Basic Medical Science","place":["Soochow University, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchuan","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Topgene Xinsheng Biotechnology Co., Ltd, No. 41, Great Health Industrial Park, South of the Optics Valley, Jiangxia District, Wuhan","place":["Hubei Province, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Topgene Xinsheng Biotechnology Co., Ltd, No. 41, Great Health Industrial Park, South of the Optics Valley, Jiangxia District, Wuhan","place":["Hubei Province, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjun","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01nv7k942","id-type":"ROR","asserted-by":"publisher"}],"name":"Hebei General Hospital","place":["Shijiazhuang City, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Yuhui Pharmaceutical Technology (Group) Co., Ltd.","place":["Shanghai, People\u2019s Republic of 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