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These cells express the voltage-gated sodium channel Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7, which is a validated pain target. Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 deficiency leads to pain insensitivity, whereas Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 gain-of-function mutants are associated with chronic pain. During differentiation, the sensory neurons start spontaneous action potential firing around day 22, with increasing firing rate until day 40. Here, we used CRISPR\/Cas9 genome editing to generate a HA-tag Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 to follow its expression during differentiation. We used two protocols to generate sensory neurons: the classical small molecule approach and a directed differentiation methodology and assessed surface Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 expression by Airyscan high-resolution microscopy. Our results show that maturation of at least 49\u00a0days is necessary to observe robust Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 surface expression in both protocols. Electric activity of the sensory neurons precedes Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 surface expression. A clinically effective Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 blocker is still missing, and we expect this iPS cell model system to be useful for drug discovery and disease modeling.\n                  <\/jats:p>","DOI":"10.1007\/s00424-024-02945-w","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T14:05:57Z","timestamp":1711548357000},"page":"975-992","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The pain target NaV1.7 is expressed late during human iPS cell differentiation into sensory neurons as determined in high-resolution imaging"],"prefix":"10.1007","volume":"476","author":[{"given":"Yi","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachna","family":"Balaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo A. Szymanski","family":"de Toledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hautvast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin B.","family":"Kesdo\u011fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannis","family":"K\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zenke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Neureiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Lampert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"issue":"5","key":"2945_CR1","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/S0959-4388(99)00015-X","volume":"9","author":"DJ Anderson","year":"1999","unstructured":"Anderson DJ (1999) Lineages and transcription factors in the specification of vertebrate primary sensory neurons. 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Reprogramming was not part of this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent of participation"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors read and revised the final manuscript. The authors declare that they have no competing interests. AL has a consultancy agreement and a research contract with Gr\u00fcnenthal. There were no conflicts of interest in preparing the manuscript, including financial, institutional and other relationships that might have led to bias.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}