{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:34:40Z","timestamp":1781670880425,"version":"3.54.5"},"reference-count":23,"publisher":"SAGE Publications","issue":"19-20","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy causing progressive vision loss due to mutations in the\n                    <jats:italic toggle=\"yes\">CHM<\/jats:italic>\n                    gene, leading to Rab escort protein 1 loss of function. CHM disease is characterized by a progressive degeneration of the choroid, the retinal pigment epithelium (RPE), and the retina. The RPE is a monolayer of polarized cells that supports photoreceptors, providing nutrients, growth factors, and ions, and removes retinal metabolism waste products, having a central role in CHM pathogenesis. Commonly used models such as ARPE-19 cells do not reproduce accurately the nature of RPE cells. Human induced pluripotent stem cells (hiPSCs) can be differentiated into RPE cells (hiPSC-RPE), which mimic key features of native RPE, being more suited to study retinal diseases. Therefore, we took advantage of hiPSCs to generate new human-based CHM models. Two isogenic hiPSC lines were generated through CRISPR\/Cas9: a CHM knock-out line from a healthy donor and a corrected CHM patient line using a knock-in approach. The differentiated hiPSC-RPE lines exhibited critical morphological and physiological characteristics of native RPE, including the presence of the tight junction markers Claudin-19 and Zonula Occludens-1, phagocytosis of photoreceptor outer segments, pigmentation, a postmitotic state, and the characteristic polygonal shape. In addition, all the studied cells were able to form retinal organoids. This work resulted in the establishment of isogenic hiPSC lines, representing a new and important CHM cellular model. To our knowledge, this is the first time that isogenic cell lines have been developed to model CHM disease, providing a valuable tool for studying the mechanisms at the onset of RPE degeneration.\n                  <\/jats:p>","DOI":"10.1089\/scd.2024.0105","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T11:06:38Z","timestamp":1722337598000},"page":"528-539","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Modeling Choroideremia Disease with Isogenic Induced Pluripotent Stem Cells"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7920-9477","authenticated-orcid":false,"given":"Ana Fragoso","family":"Fonseca","sequence":"first","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Coelho","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda Lopes-","family":"da-Silva","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa","family":"Lemos","sequence":"additional","affiliation":[{"name":"Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Hall","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Oliveira","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Sofia","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Tenreiro","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel C.","family":"Seabra","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."},{"name":"Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Antas","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas, NMS | FCM, Universidade Nova de Lisboa, Lisboa, Portugal."},{"name":"Champalimaud Research, Champalimaud Foundation, Lisbon, 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