Academic Journal
Single-cell transcriptomic analysis reveals a metastasis-associated PCSK1+ neuroendocrine subpopulation in pancreatic neuroendocrine tumors.
| Τίτλος: | Single-cell transcriptomic analysis reveals a metastasis-associated PCSK1+ neuroendocrine subpopulation in pancreatic neuroendocrine tumors. |
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| Συγγραφείς: | Yin X; Department of Gastroenterology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Li X; Medical Record Room, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Mi L; Department of Gastroenterology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Hou J; Department of Gastroenterology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Yin F; Department of Gastroenterology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. |
| Πηγή: | Journal of neuroendocrinology [J Neuroendocrinol] 2025 Nov; Vol. 37 (11), pp. e70084. Date of Electronic Publication: 2025 Aug 16. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley & Sons Country of Publication: United States NLM ID: 8913461 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2826 (Electronic) Linking ISSN: 09538194 NLM ISO Abbreviation: J Neuroendocrinol Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2010->: Malden, MA : Wiley & Sons Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989- |
| Ιατρικοί όροι (MeSH): | Neuroendocrine Tumors*/genetics , Neuroendocrine Tumors*/pathology , Neuroendocrine Tumors*/metabolism , Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/metabolism , Neuroendocrine Cells*/metabolism , Neuroendocrine Cells*/pathology , Proprotein Convertase 1*/metabolism , Proprotein Convertase 1*/genetics , Transcriptome*, Liver Neoplasms/secondary ; Liver Neoplasms/genetics ; Humans ; Single-Cell Analysis ; Gene Expression Profiling ; Neoplasm Metastasis |
| Περίληψη: | Pancreatic neuroendocrine tumors (PNETs) are uncommon malignancies characterized by significant clinical heterogeneity and a pronounced tendency for liver metastasis. Despite this, the cellular mechanisms driving PNET progression remain inadequately elucidated, especially concerning neuroendocrine subpopulations. We analyzed publicly available single-cell RNA sequencing (scRNA-seq) data from 27 samples, including adjacent normal tissues (NT), primary tumors (PT), and hepatic metastases (HM), to explore the heterogeneity of neuroendocrine cells. Our downstream analyses encompassed copy number variation (CNV) inference, pseudotime trajectory modeling using CytoTRACE2 and Monocle3, Single-Cell Regulatory Network Inference and Clustering (SCENIC), cell-cell communication analysis via CellChat, and external validation with bulk RNA-seq datasets. We identified a distinct PCSK1+ neuroendocrine cell subpopulation, predominantly found in HM, which exhibited a high CNV burden, low differentiation potential, and significant transcriptional divergence from the NEUROD1+ neuroendocrine cells prevalent in primary tumors. The trajectory analysis delineated a developmental continuum commencing from the NEUROD1+ subpopulation and culminating in the PCSK1+ subpopulation. SCENIC analysis identified ATF6 as a pivotal transcriptional regulator within the PCSK1+ subpopulation, while KEGG enrichment of its target genes indicated involvement in stress-related signaling pathways. Furthermore, cell-cell communication analysis demonstrated that fibroblasts were the predominant signaling source to the PCSK1+ subpopulation in both primary tumors (PT) and hepatic metastases (HM), with conserved ligand-receptor interactions, including the CD99-CD99 and collagen-integrin axes. Our study identifies a metastasis-enriched, terminally differentiated PCSK1+ subpopulation and elucidates its potential regulatory and microenvironmental characteristics. These findings enhance our understanding of the cellular states linked to the progression of PNETs and lay the groundwork for subsequent mechanistic investigations. (© 2025 British Society for Neuroendocrinology.) |
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| Grant Information: | 22377788D S&T Program of Hebei |
| Contributed Indexing: | Keywords: PCSK1+ subpopulation; liver metastasis; neuroendocrine subpopulations; pancreatic neuroendocrine tumors; single‐cell RNA sequencing |
| Substance Nomenclature: | EC 3.4.21.93 (Proprotein Convertase 1) |
| Entry Date(s): | Date Created: 20250816 Date Completed: 20251102 Latest Revision: 20260603 |
| Update Code: | 20260604 |
| DOI: | 10.1111/jne.70084 |
| PMID: | 40817830 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1365-2826 |
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| DOI: | 10.1111/jne.70084 |