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We performed detailed morphological and molecular analyses, including bulk and single cell RNA sequencing, of generated lung organoids and evaluated the quality and robustness of our model as a potential in vitro platform for lung diseases, namely radiation-induced lung injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A matrix-free method for differentiation of iPSCs can be used to obtain lung organoids that morphologically reflect the target tissue of the human lung very well, especially with regard to the cellular composition. The different cellular fates were investigated following the genotoxic stress induced by radiation and revealed further insights in the radiation-sensitivity of the different lung cells. Finally, we provide cellular gene sets found to be induced in the different lung organoid cellular subsets after irradiation, which could be used as additional RT response and particularly senescence gene sets in future studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By establishing these free-floating LuOrgs for the investigation of cancer therapeutic approaches as a new and patient-oriented in vitro platform particularly in experimental radiooncology, not only a reduction in the number of experimental animals, but also an adequately and meaningfully replacement of corresponding animal experiments can be achieved.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-024-04106-3","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T13:23:30Z","timestamp":1734528210000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury"],"prefix":"10.1186","volume":"15","author":[{"given":"Bettina","family":"Budeus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Kroepel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Marie","family":"Stasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-443X","authenticated-orcid":false,"given":"Diana","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"issue":"15","key":"4106_CR1","doi-asserted-by":"publisher","first-page":"2756","DOI":"10.1016\/j.cell.2022.06.051","volume":"185","author":"NS Corsini","year":"2022","unstructured":"Corsini NS, Knoblich JA. 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Total RNA from healthy human lung tissue was used as control [\n                      \n                      ,\n                      \n                      ]. These experiments were performed in strict accordance with local guidelines and regulations. Samples were collected in close cooperation with the local biobank (Westdeutsche Biobank Essen). Human tissue samples were analyzed anonymously. Written informed consent (17-7454-BO; title: \u201cRetrospective determination of the expression of radiation-induced normal tissue toxicity factors with the potential for targeted modulation of radiation effects in normal and tumor tissue\u201d; approval date 15.03.2017) was obtained from the Ethikkommission of the University Medical Faculty, Essen, Germany (\u201cEthik-Kommission der Medizinischen Fakult\u00e4t der Universit\u00e4t Duisburg-Essen\u201d). iPSC lines were derived from indicated companies with material transfer agreement (MTA).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare that they have not use AI-generated work in this manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Artificial Intelligence (AI)"}}],"article-number":"468"}}