Single-cell sequencing identifies differentiation-related markers for molecular classification and recurrence prediction of PitNET

Zhang, Qilin; Yao, Boyuan; Long, Xin; Chen, Zhengyuan; He, Min; Wu, Yang; Qiao, Na; Ma, Zengyi; Zhao, Yupei; Zhang, Yichao; Yao, Shun; Wang, Ye; Cheng, Haixia; Chen, Hong; Ye, Hongying; Wang, Yongfei; Li, Yimin; Chen, Jianhua; Zhang, Zhaoyun; Guo, Fan; Zhao, Yao

doi:10.1016/j.xcrm.2023.100934

Cited by 23 publications

(17 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we further highlighted the tumor heterogeneity and TIME of three transcription factor(TF)-based lineages in PitNETs from a single-cell perspective. Our results complement previous studies concerning the heterogeneity of different lineages in PitNETs [ 3 , 5 , 6 ]. We identified that different lineages of PitNET not only have distinct characteristics in TF-related transcriptomic profiles and functional modules but also exhibit genetic variation and CNVs.…”

Section: Discussionsupporting

confidence: 91%

“…Among these, the POU1F1 + tumor cells demonstrated intracellular protein trafficking and extracellular protein release. This aligned with the clinical manifestation of abnormally high secretion of certain hormones in the PIT1 lineage [ 5 ]. A recent study also supported these findings and demonstrated an inverse correlation between differentiation status and recurrence within the PIT1/TPIT lineage compared to the SF1 lineage [ 57 ].…”

Section: Discussionsupporting

confidence: 52%

“…This aligned with the clinical manifestation of abnormally high secretion of certain hormones in the PIT1 lineage [ 5 ]. A recent study also supported these findings and demonstrated an inverse correlation between differentiation status and recurrence within the PIT1/TPIT lineage compared to the SF1 lineage [ 57 ]. In particular, we combined 23 single-cell and 365 in-house bulk RNA-seq to reveal that all 3 PitNET subtypes have distinct immune-infiltrated patterns.…”

Section: Discussionsupporting

confidence: 52%

“…However, the specific function and heterogeneity of these immune cell subtypes in PitNETs remain poorly understood, which can help identify new therapeutic targets. Some studies have endeavored to characterize the immune microenvironment of PitNETs using immunohistochemistry (IHC) [ 16 ], flow cytometry (FC) [ 19 ], and RNA-seq (including both bulk RNA-seq and single-cell RNA-seq) [ 3 , 5 – 7 , 9 ]. Macrophages, a highly heterogeneous group of immune cells, have many functions, including phagocytosis, antigen presentation, cytokine production, and tissue remodeling [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Lin,

Dai,

Han

et al. 2024

Genome Med

View full text Add to dashboard Cite

Background Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. Methods The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. Results The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. Conclusions In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 52%

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Lin,

Dai,

Han

et al. 2024

Genome Med

View full text Add to dashboard Cite

show abstract

“…Taken together, our results were convincing the cultured hPASCs possessed the characteristics of TSCs. Recently single-cell sequencing of pituitary adenoma con rmed the presence of TSCs in the tumor, despite in a non-proliferative status [10]. We speculated other factors may be required to drive the hPASCs into the cell cycle and differentiation.…”

Section: Discussionmentioning

confidence: 85%

Transcriptional Profiling of Pituitary Adenoma Stem Cells: Unveiling the Pivotal Role of CXCR4 in Tumorigenesis and Clinical Applications

Yuan,

Li,

Sui

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Growth hormone-secreting pituitary adenoma (GHPA) is characterized by excessive growth hormone production and leads to clinical manifestations like acromegaly. The molecular intricacies underpinning the tumorigenesis of this neoplasm remain largely elusive, with tumor stem cells postulated to play a significant role. Method Human pituitary adenoma stem cells (hPASCs) were extracted and cultured from eight GHPA clinical samples. RNA-sequencing was performed to discern genetic disparities between hPASCs and matched bulk tumor samples. Primary clusters of protein-protein interaction network were mapped using MCODE plugin in Cytoscape. The functional role of CXCR4 was assessed by both siRNA and antagonist AMD3465 in GH3 cells or primary hPASCs. Seven GHPA patients received PET/CT scan using CXCR4-based tracer 68Ga-pentixafor. Results HPASC culture was established and verified. A total of 685 differentially expressed genes were identified between hPASC and bulk tumor samples. Four primary protein-protein interaction network clusters were predicted, each demonstrating distinct biological functions. CXCR4 knockdown significantly attenuated GH3 cell proliferation and the hormone production. CXCR4 antagonist AMD3465 markedly reduced cell proliferation during differentiation of hPASCs. PET/CT imaging showed 68Ga-pentixafor can be a superior tracer in the detection of GHPA in the patients. Conclusion This study delivers a comprehensive genetic profiling of hPASCs and substantiates the critical role of CXCR4 in tumorigenesis, highlighting its considerable diagnostic potential in the translational research.

show abstract

Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single‐cell transcriptomics

Wang,

Li,

Guo

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

BackgroundPituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood.MethodsIn this study, we performed integrative spatial transcriptomics (ST) and single‐cell RNA sequencing (scRNA‐seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics.ResultsBy analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNVhigh and CNVlow areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNVhigh area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment.ConclusionIn summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA‐seq for the first time. This study provides a strong theoretical foundation to comprehensively understand the crucial mechanisms involved in tumour progression and develop new strategies to treat somatotroph PitNETs.Key points The first‐ever visualization of cellular distributions in normal and tumor pituitary tissues. The inter‐ and intra‐tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed. Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.

show abstract

Single-cell sequencing identifies differentiation-related markers for molecular classification and recurrence prediction of PitNET

Cited by 23 publications

References 85 publications

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Transcriptional Profiling of Pituitary Adenoma Stem Cells: Unveiling the Pivotal Role of CXCR4 in Tumorigenesis and Clinical Applications

Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single‐cell transcriptomics

Contact Info

Product

Resources

About