{"doi":"10.7554/elife.73511","title":"P2RY14 cAMP signaling regulates Schwann cell precursor self-renewal, proliferation, and nerve tumor initiation in a mouse model of neurofibromatosis","abstract":"Neurofibromatosis type 1 (NF1) is characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) show deregulated RAS signaling. NF1 is also implicated in regulation of cAMP. We identified the G-protein-coupled receptor (GPCR) P2ry14 in human neurofibromas, neurofibroma-derived SC precursors (SCPs), mature SCs, and mouse SCPs. Mouse Nf1-/- SCP self-renewal was reduced by genetic or pharmacological inhibition of P2ry14. In a mouse model of NF1, genetic deletion of P2ry14 rescued low cAMP signaling, increased mouse survival, delayed neurofibroma initiation, and improved SC Remak bundles. P2ry14 signals via G i to increase intracellular cAMP, implicating P2ry14 as a key upstream regulator of cAMP. We found that elevation of cAMP by either blocking the degradation of cAMP or by using a P2ry14 inhibitor diminished NF1 -/- SCP self-renewal in vitro and neurofibroma SC proliferation in in vivo. These studies identify P2ry14 as a critical regulator of SCP self-renewal, SC proliferation, and neurofibroma initiation.","journal":"eLife","year":2022,"id":261846,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653087,"name":"Jianqiang Wu","orcid":"0000-0002-4239-5659","position":1,"is_corresponding":false},{"id":917108,"name":"Robert A Coover","orcid":null,"position":2,"is_corresponding":false},{"id":917109,"name":"Tilat A Rizvi","orcid":null,"position":3,"is_corresponding":false},{"id":917110,"name":"Katherine E Chaney","orcid":null,"position":4,"is_corresponding":false},{"id":392870,"name":"Ramya Ravindran","orcid":"0000-0002-1058-5706","position":5,"is_corresponding":false},{"id":917111,"name":"Jose A Cancelas","orcid":null,"position":6,"is_corresponding":false},{"id":917112,"name":"Robert J Spinner","orcid":null,"position":7,"is_corresponding":false},{"id":345879,"name":"Nancy Ratner","orcid":"0000-0001-5030-9354","position":8,"is_corresponding":false},{"id":699271,"name":"Jennifer Patritti Cram","orcid":"0000-0001-5971-0849","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:26:16.663144Z","pmid":"35311647","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":[]}