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人垂体类器官：通过单细胞RNA测序和空间转录组测序解析转录图谱，深入了解SOX3在垂体发育中的作用

Human Pituitary Organoids: Transcriptional Landscape Deciphered by scRNA-Seq and Stereo-Seq, with Insights into SOX3's Role in Pituitary Development.

作者信息

Wang Shengjie, Jiang Deyue, Xiao Yan, Qin Qiaozhen, Zhang Heyang, Ye Lingtong, Jin Jide, Jiang Xiaoxia, Guo Qinghua

机构信息

Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.

Beijing Institute of Basic Medical Sciences, 27 Taiping Road of Haidian District, Beijing, 100850, China.

出版信息

Adv Sci (Weinh). 2025 Apr;12(14):e2414230. doi: 10.1002/advs.202414230. Epub 2025 Feb 14.

DOI:10.1002/advs.202414230
PMID:39951008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11984888/
Abstract

The 3D human pituitary organoid represents a promising laboratory model for investigating human pituitary diseases. Nonetheless, this technology is still in its nascent stage, with uncertainties regarding the cellular composition, intercellular interactions, and spatial distribution of the human pituitary organoids. To address these gaps, the culture conditions are systematically adjusted and the efficiency of induced pluripotent stem cells' (iPSCs') differentiation into pituitary organoids is successfully improved, achieving results comparable to or exceeding those of previous studies. Additionally, single-cell RNA-sequencing (scRNA-seq) and stereomics sequencing (Stereo-seq) are performed on the pituitary organoids for the first time, and unveil the diverse cell clusters, intricate intercellular interactions, and spatial information within the organoids. Furthermore, the SOX3 gene interference impedes the iPSCs' differentiation into pituitary organoids, thereby highlighting the potential of pituitary organoids as an ideal experimental model. Altogether, the research provides an optimized protocol for the human pituitary organoid culture and a valuable transcriptomic dataset for future explorations, laying the foundation for subsequent research in the field of pituitary organoids or pituitary diseases.

摘要

三维人垂体类器官是研究人类垂体疾病的一个很有前景的实验室模型。尽管如此，这项技术仍处于起步阶段，人垂体类器官的细胞组成、细胞间相互作用和空间分布尚存在不确定性。为了填补这些空白，系统地调整了培养条件，成功提高了诱导多能干细胞（iPSC）分化为垂体类器官的效率，取得了与以往研究相当或更好的结果。此外，首次对垂体类器官进行了单细胞RNA测序（scRNA-seq）和空间组学测序（Stereo-seq），揭示了类器官内不同的细胞簇、复杂的细胞间相互作用和空间信息。此外，SOX3基因干扰阻碍了iPSC向垂体类器官的分化，从而突出了垂体类器官作为理想实验模型的潜力。总之，该研究为人垂体类器官培养提供了优化方案，并为未来探索提供了有价值的转录组数据集，为垂体类器官或垂体疾病领域的后续研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/e5d7c5699309/ADVS-12-2414230-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/6edebf62f37c/ADVS-12-2414230-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/eafd6614a362/ADVS-12-2414230-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/e5d7c5699309/ADVS-12-2414230-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/6edebf62f37c/ADVS-12-2414230-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/3fe292fbb4dd/ADVS-12-2414230-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/3054f2d61c11/ADVS-12-2414230-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735b/11984888/e5d7c5699309/ADVS-12-2414230-g007.jpg

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本文引用的文献

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Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction.推进用于组织再生和生物功能重建的类器官工程
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Pituitary stem cells: past, present and future perspectives.垂体干细胞：过去、现在和未来的展望。
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Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.时空转录组图谱揭示了人类大脑发育的区域特化。
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Pituitary crosstalk with bone, adipose tissue and brain.垂体与骨、脂肪组织和脑的相互作用。
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Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity.新型人类多能干细胞衍生的下丘脑类器官表现出细胞多样性。
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