{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:12:16Z","timestamp":1773011536456,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002830","name":"Centre National d\u2019Etudes Spatiales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002830","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patient\u2010derived neural organoids (NOs) have emerged as powerful tools for modeling human neurodevelopmental disorders, especially when animal models are unavailable or fail to recapitulate human\u2010specific cortical development. However, significant variability in differentiation potential, even among healthy donor lines, and especially in fragile patient\u2010derived induced pluripotent stem cells (iPSCs), poses major methodological challenges. Protocols that succeed in one line may fail in others, leading to poor organoid formation, reduced growth, impaired neuroepithelial patterning, or complete failure to generate neural tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>By systematically comparing multiple published protocols, we identified key sources of variability and ultimately developed optimized protocols for generating both whole\u2010brain (WB) and cortical organoids (CO) from human iPSCs (hiPSCs), including lines from progeroid Cockayne syndrome patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Through iterative refinement of critical parameters, including cell seeding density, Matrigel incorporation, and timing and type of pathway inhibition, we achieved consistent organoid growth and structural organization across all tested lines. The resulting pipeline is adaptable and can be further tailored for newly derived or particularly challenging hiPSC lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, this methodological framework enables robust and reproducible generation of NOs from genetically diverse hiPSC sources, providing a reliable platform for studying human neurodevelopment and disease mechanisms in progeroid and other patient\u2010specific contexts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/boc.70051","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:28:55Z","timestamp":1772990935000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Robust Methodological Framework for Generating Whole\u2010Brain and Cortical Organoids From Diverse Healthy\u2010 and Patient\u2010Derived Induced Pluripotent Stem Cell Lines"],"prefix":"10.1111","volume":"118","author":[{"given":"Tara","family":"Fournier","sequence":"first","affiliation":[{"name":"Department of Developmental and Stem Cell Biology Molecular Mechanisms of Pathological and Physiological Ageing, UMR3738 CNRS, Institut Pasteur  Paris France"},{"name":"Coll\u00e8ge Doctoral Sorbonne Universit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Department of Developmental and Stem Cell Biology Molecular Mechanisms of Pathological and Physiological Ageing, UMR3738 CNRS, Institut Pasteur  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Montagne","sequence":"additional","affiliation":[{"name":"Department of Developmental and Stem Cell Biology Molecular Mechanisms of Pathological and Physiological Ageing, UMR3738 CNRS, Institut Pasteur  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cimmaruta","sequence":"additional","affiliation":[{"name":"Department of Developmental and Stem Cell Biology Molecular Mechanisms of Pathological and Physiological Ageing, UMR3738 CNRS, Institut Pasteur  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miria","family":"Ricchetti","sequence":"additional","affiliation":[{"name":"Department of Developmental and Stem Cell Biology Molecular Mechanisms of Pathological and Physiological Ageing, UMR3738 CNRS, Institut Pasteur  Paris 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