耶鲁大学医学院In-Hyun Park团队取得一项新突破。他们的最新研究提出了可产生褪黑素用于疾病建模的人类松果体类器官构建。2025年12月30日出版的《细胞—干细胞》杂志发表了这项成果。

为了克服这个问题，该研究团队从多能干细胞中培养了人类松果体类器官（hPGOs），模拟了松果体的发育和功能。单细胞RNA测序揭示了不同的成熟和发育的松果体细胞群体，其转录组谱与体内松果体非常相似。hPGOs产生褪黑激素，表达肾上腺素能受体，并对去甲肾上腺素作出反应，模拟生理调节。为了模拟疾病相关的损伤，研究组从Angelman综合征（AS）患者来源的iPSCs中生成了hPGOs，这些iPSCs表现出松果体细胞分化被破坏，褪黑激素合成明显减少，反映了AS相关的发育病理。此外，移植的hPGOs恢复了松果体切除小鼠的循环褪黑激素，证明了它们在细胞治疗方法中的潜力。这些发现奠定了hPGOs作为探索松果体发育、昼夜节律调节及其在神经发育和睡眠相关疾病中的破坏的基本平台。

研究人员表示，松果体通过褪黑激素的产生调节昼夜节律，但人体研究受到组织接触不足的限制。

附：英文原文

Title: Generation of human pineal gland organoids with melatonin production for disease modeling

Author: Ferdi Ridvan Kiral, Woo Sub Yang, Onur Iyilikci, Xiaona Lu, Jonghun Kim, Mu Seog Choe, Cynthia Lo, Mei Zhong, Kun-Yong Kim, Yong-Hui Jiang, In-Hyun Park

Issue&Volume: 2025-12-30

Abstract: The pineal gland regulates circadian rhythms through melatonin production, yet human studies are limited by poor tissue access. To overcome this, we developed human pineal gland organoids (hPGOs) from pluripotent stem cells, modeling pineal development and function. Single-cell RNA sequencing revealed distinct mature and developing pinealocyte populations with transcriptomic profiles closely resembling the in vivo pineal gland. hPGOs produce melatonin, express adrenergic receptors, and respond to noradrenaline, mimicking physiological regulation. To model disease-related impairments, we generated hPGOs from Angelman syndrome (AS) patient-derived iPSCs, which exhibit disrupted pinealocyte differentiation and markedly reduced melatonin synthesis, reflecting AS-related developmental pathology. Additionally, transplanted hPGOs restored circulating melatonin in pinealectomized mice, demonstrating their potential for cell-therapy approaches. These findings establish hPGOs as a robust platform for probing pineal development, circadian regulation, and their disruption in neurodevelopmental and sleep-related disorders.

DOI: 10.1016/j.stem.2025.12.004

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00438-2