Single-cell and spatial transcriptome analyses reveal tumor heterogeneity and immune remodeling involved in pituitary neuroendocrine tumor progression

Wan Su, Zhang Ye, Jifang Liu, Kan Deng, Jinghua Liu, Huijuan Zhu, Lian Duan, Chen Shi, Linjie Wang, Yuxing Zhao, Fengying Gong, Yi Zhang, Bo Hou, Hui You, Feng Feng, Qing Ling, Yu Xiao, Yongdong Guo, Wenyi Fan, Sumei Zhang, Zixin Zhang, Xiaomin Hu (), Yong Yao (), Chunhong Zheng () and Lin Lu ()
Additional contact information
Wan Su: Chinese Academy of Medical Sciences & Peking Union Medical College
Zhang Ye: Chinese Academy of Medical Sciences & Peking Union Medical College
Jifang Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Kan Deng: Chinese Academy of Medical Sciences & Peking Union Medical College
Jinghua Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Huijuan Zhu: Chinese Academy of Medical Sciences & Peking Union Medical College
Lian Duan: Chinese Academy of Medical Sciences & Peking Union Medical College
Chen Shi: Chinese Academy of Medical Sciences & Peking Union Medical College
Linjie Wang: Chinese Academy of Medical Sciences & Peking Union Medical College
Yuxing Zhao: Chinese Academy of Medical Sciences & Peking Union Medical College
Fengying Gong: Chinese Academy of Medical Sciences & Peking Union Medical College
Yi Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Bo Hou: Chinese Academy of Medical Sciences & Peking Union Medical College
Hui You: Chinese Academy of Medical Sciences & Peking Union Medical College
Feng Feng: Chinese Academy of Medical Sciences & Peking Union Medical College
Qing Ling: Chinese Academy of Medical Sciences & Peking Union Medical College
Yu Xiao: Chinese Academy of Medical Sciences & Peking Union Medical College
Yongdong Guo: Peking University
Wenyi Fan: Peking University Cancer Hospital & Institute
Sumei Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Zixin Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiaomin Hu: Chinese Academy of Medical Sciences & Peking Union Medical College
Yong Yao: Chinese Academy of Medical Sciences & Peking Union Medical College
Chunhong Zheng: Peking University Cancer Hospital & Institute
Lin Lu: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Pituitary neuroendocrine tumors (PitNETs) can be invasive or aggressive, yet the mechanisms behind these behaviors remain poorly understood, impeding treatment advancements. Here, we integrat single-cell RNA sequencing and spatial transcriptomics, analyzing over 177,000 cells and 35,000 spots across 57 tissue samples. This comprehensive approach facilitates the identification of PitNETs tumor populations and characterizes the reconfiguration of the tumor microenvironment (TME) as PitNETs progress and invade. We trace the trajectory of TPIT-lineage PitNETs and identify an aggressive tumor cluster marked by elevated p53-mediated proliferation and a higher Trouillas classification, both associated with tumor progression. Additionally, we document the heterogeneity of immune stromal cells within PitNETs, particularly noting the enrichment of SPP1+ tumor associated macrophages (TAMs) in invasive tumors. These TAMs facilitate tumor invasion through the SPP1-ITGAV/ITGB1 signaling pathway. Our in-depth single-cell and spatial analysis of PitNETs uncovers the molecular dynamics within the TME, suggesting potential targets for therapeutic intervention.

Date: 2025
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DOI: 10.1038/s41467-025-60028-5

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