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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\n                    <jats:italic>Nf1-\/-<\/jats:italic>\n                    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\n                    <jats:sub>i<\/jats:sub>\n                    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\n                    <jats:italic>NF1<\/jats:italic>\n                    -\/- 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.\n                  <\/jats:p>","DOI":"10.7554\/elife.73511","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T09:00:51Z","timestamp":1647853251000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73511","source":"Crossref","is-referenced-by-count":17,"title":["P2RY14 cAMP signaling regulates Schwann cell precursor self-renewal, proliferation, and nerve tumor initiation in a mouse model of neurofibromatosis"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5971-0849","authenticated-orcid":true,"given":"Jennifer","family":"Patritti Cram","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01hcyya48","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Experimental Hematology and Cancer Biology, Cancer & Blood Diseases Institute, Cincinnati Children's Hospital Medical 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