{"doi":"10.1016/j.celrep.2025.116500","title":"Single-cell RNA-seq of small-intestinal neuroendocrine tumors reveals the cell of origin and gene expression of early tumor development","abstract":"Patients with a hereditary form of small-intestinal neuroendocrine tumors (SI-NETs) present with multiple synchronous tumors and precursors at various stages. Using this germline trait, single-cell RNA sequencing is performed to define the cell-of-origin and gene-expression trajectory in early tumor development. A subset of CES1(+), LCN15(-) enterochromaffin (EC) cells, residing at +4 position and below in the crypts, distinct from EC cells migrating up the villi, emerges as the putative SI-NET origin. PRODH2 is identified as a key biomarker for precursor cells, revealing stage-specific gene expression linked to early tumor development. From precursor to fully developed tumors, notable changes include the up-regulation of UCHL1 and MBD3L2, as well as the significant down-regulation of cell-cycle inhibitory genes, CDKN1A, CDKN1C, and CDKN2B, which play roles in cell survival and tumorigenesis. The current study provides insight into SI-NET initiation and progression, offering potential advancements in diagnosis, prevention, and treatment.","journal":"Cell Reports","year":2025,"id":527377,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9176,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1404697,"name":"Joanne Forbes","orcid":null,"position":1,"is_corresponding":false},{"id":383897,"name":"Cihan Oguz","orcid":"0000-0002-2860-3546","position":2,"is_corresponding":false},{"id":956701,"name":"Paul Schaughency","orcid":"0000-0002-3358-2102","position":3,"is_corresponding":false},{"id":809583,"name":"Gustavo Gutierrez-Cruz","orcid":null,"position":4,"is_corresponding":false},{"id":844372,"name":"Faiza Naz","orcid":"0000-0002-7510-4491","position":5,"is_corresponding":false},{"id":218255,"name":"Stephen R. Brooks","orcid":"0000-0001-5592-5332","position":6,"is_corresponding":false},{"id":640119,"name":"Stefania Dell’Orso","orcid":"0000-0002-1306-2820","position":7,"is_corresponding":false},{"id":271933,"name":"Pradeep K. Dagur","orcid":"0000-0002-4491-0853","position":8,"is_corresponding":false},{"id":1404698,"name":"Jianying Feng","orcid":null,"position":9,"is_corresponding":false},{"id":311841,"name":"Xilin Zhao","orcid":"0000-0001-8375-8658","position":10,"is_corresponding":false},{"id":755530,"name":"Marybeth S. Hughes","orcid":null,"position":11,"is_corresponding":false},{"id":238362,"name":"Naris Nilubol","orcid":"0000-0002-7348-7804","position":12,"is_corresponding":false},{"id":563532,"name":"Stephen A. Wank","orcid":"0000-0002-9608-547X","position":13,"is_corresponding":false},{"id":1404073,"name":"Yoshitatsu Sei","orcid":"0000-0002-3073-5126","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:50:39.280101Z","pmid":"41175375","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}