Single-cell multi-omic and spatial landscape of primate pineal gland reveals circadian and melatonin regulatory architecture

ABSTRACT: The mammalian pineal gland maintains circadian rhythms and homeostasis by secreting melatonin. However, the lack of a cell-resolved regulatory map limits our understanding of how these neuroendocrine functions are orchestrated in primates. Here, we constructed a multi-omics atlas of the Macaca fascicularis pineal gland 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. Co-expression networks further identified core modules and regulatory hubs—including CRX/OTX2, LHX4, and RORA—that integrate these circadian and light-responsive signals. Cell-cell communication analysis identified signaling axes, such as PTN-ALK/SDC2, RA-RORB, and NRG1-ERBB4, 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 MEIS1-linked elements, while bipolar disorder-associated loci highlighted candidate genes RDH12 and SDK2. Overall, this study reveals the cellular diversity and spatial regulatory logic of the primate pineal gland, providing a foundation for investigating circadian and neuroendocrine regulation in health and disease.

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE324158 | GEO | 2026/04/23

REPOSITORIES: GEO