Author
Listed:
- 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
Peking University)
- 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
Peking University)
- Lin Lu
(Chinese Academy of Medical Sciences & Peking Union Medical College)
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.
Suggested Citation
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, 2025.
"Single-cell and spatial transcriptome analyses reveal tumor heterogeneity and immune remodeling involved in pituitary neuroendocrine tumor progression,"
Nature Communications, Nature, vol. 16(1), pages 1-20, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60028-5
DOI: 10.1038/s41467-025-60028-5
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