Single-cell and spatial transcriptome analyses reveal tumor heterogeneity and immune remodeling involved in pituitary neuroendocrine tumor progression
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.
Authors
- Chunhong Zheng (ORCID: https://orcid.org/0009-0004-9991-9080)
- Xiao-Min Hu (ORCID: https://orcid.org/0000-0001-5746-4242)
- Bo Hou (ORCID: https://orcid.org/0000-0001-7609-673X)
- Yongdong Guo
- Jifang Liu (ORCID: https://orcid.org/0009-0002-1174-6193)
- Qing Ling (ORCID: https://orcid.org/0000-0001-9667-4138)
- Huijuan Zhu (ORCID: https://orcid.org/0000-0001-5172-6870)
- Shi Chen (ORCID: https://orcid.org/0000-0002-8965-1015)
- Wenyi Fan (ORCID: https://orcid.org/0000-0002-7875-7404)
- Fengying Gong (ORCID: https://orcid.org/0000-0002-6361-3811)
- Lian Duan (ORCID: https://orcid.org/0000-0001-7210-056X)
- Wan Su
- Lin Lü (ORCID: https://orcid.org/0000-0003-3379-8277)
- Kan Deng (ORCID: https://orcid.org/0000-0001-9571-3705)
- Feng Feng (ORCID: https://orcid.org/0000-0002-3960-7761)
- Yong Yao (ORCID: https://orcid.org/0000-0001-6982-8832)
- Sumei Zhang
- Yu Xiao
- Yuxing Zhao
- Zixin Zhang (ORCID: https://orcid.org/0000-0002-1135-6606)
- Jinghua Liu (ORCID: https://orcid.org/0000-0002-2358-2600)
- Hui You
- Yi Zhang (ORCID: https://orcid.org/0000-0001-5914-8024)
- Linjie Wang (ORCID: https://orcid.org/0000-0003-3227-9184)
- Zhang Ye (ORCID: https://orcid.org/0000-0003-3495-5596)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Peking Union Medical College Hospital (CN)
- Peking University Cancer Hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1038/s41467-025-60028-5
- Citations
- 10
- Primary Topic
- Pituitary Gland Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 12.95