{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2026","publisher":"Springer Nature","file_date_updated":"2026-09-07T13:24:10Z","quality_controlled":"1","external_id":{"pmid":["42587153"]},"acknowledgement":"We thank M. L. de Guevara, S. Jayaram and A. Heger for technical assistance with mESC derivation; M. Goudarzi for assistance with organoid imaging; M. Leeb and F. Freeman for advice in culturing mESCs and organoids; S. Gobeil and L. Sweeney for reagents and advice for organoid clearing; A. Heger for mouse colony management; J. Hauser for technical assistance; the Stanford Brain Organogenesis Workshop; and all members of the Hippenmeyer laboratory for discussion and/or comments on the manuscript. This study was supported by the Scientific Service Units (SSU) of the Institute of Science and Technology, Austria through resources provided by the Imaging and Optics Facility (IOF), Laboratory Support Facility (LSF) and Preclinical Facility (PCF). M.S. received funding from the European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional funds to S.H., FWF SFB F78 Neuro Stem Modulation to S.H., and by the European Research Council (ERC) under the European Union’s Horizon 2020 Research And Innovation Program (grant agreement 725780 LinPro) to S.H. Open access funding provided by Institute of Science and Technology (IST Austria).","dataavailabilitystatement":"All data generated and analysed in this study are included in the paper, source data and/or Supplementary Tables 2 and 3. Raw sequencing data have been deposited with Gene Expression Omnibus (GEO) accession number GSE327470. Source data are provided with this paper. All scripts used to prepare data and figures for this manuscript are accessible on GitHub at https://github.com/fpauler/Temporal-Uncoupling-of-Radial-Glia-Lineage-Progression-in-Cortical-Organoid.","oa_version":"Published Version","project":[{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"OA_type":"hybrid","oa":1,"date_updated":"2026-09-07T13:29:07Z","department":[{"_id":"SiHi"}],"_id":"22753","title":"Temporal uncoupling of radial glia lineage progression in cortical organoids","scopus_import":"1","has_accepted_license":"1","month":"08","das_tickbox":"1","article_type":"original","file":[{"date_created":"2026-09-07T13:24:10Z","relation":"main_file","success":1,"file_id":"22844","date_updated":"2026-09-07T13:24:10Z","file_size":48513068,"checksum":"11383e28fc430b28d2666f73833e8b56","file_name":"2026_Nature_Stouffer.pdf","content_type":"application/pdf","access_level":"open_access","creator":"dernst"}],"abstract":[{"lang":"eng","text":"Radial glial progenitors (RGPs) produce all excitatory neurons in the developing cerebral cortex. Mosaic analysis with double markers (MADM)-based lineage tracing in vivo has revealed a quantitative framework of RGP lineage progression1. Here we established MADM technology2,3 in mouse embryonic stem cells to probe RGP lineage progression in a self-organizing cortical organoid system. We found that RGPs exhibit a high level of plasticity in proliferative potential in organoids rather than strict temporally stereotyped lineage progression as observed in vivo. RGPs in organoids showed increased lineage restriction, diminishing cell-type diversity in clones of cortical projection neurons, despite uniform single-cell transcriptional signatures of RGPs and a unitary lineage trajectory. Thus, critical non-cell-autonomous cues that are absent in self-organizing systems and/or the genuine stem cell niche are essential for faithful temporal control of RGP lineage progression and the generation of clonal cortical cell-type diversity."}],"article_processing_charge":"Yes (via OA deal)","language":[{"iso":"eng"}],"supplementarymaterial":"yes","citation":{"ama":"Stouffer MA, Miranda O, Pauler F, et al. Temporal uncoupling of radial glia lineage progression in cortical organoids. <i>Nature</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41586-026-10916-7\">10.1038/s41586-026-10916-7</a>","mla":"Stouffer, Melissa A., et al. “Temporal Uncoupling of Radial Glia Lineage Progression in Cortical Organoids.” <i>Nature</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41586-026-10916-7\">10.1038/s41586-026-10916-7</a>.","ista":"Stouffer MA, Miranda O, Pauler F, Pipicelli F, Streicher C, Cheung GT, Hippenmeyer S. 2026. Temporal uncoupling of radial glia lineage progression in cortical organoids. Nature.","apa":"Stouffer, M. A., Miranda, O., Pauler, F., Pipicelli, F., Streicher, C., Cheung, G. T., &#38; Hippenmeyer, S. (2026). Temporal uncoupling of radial glia lineage progression in cortical organoids. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-026-10916-7\">https://doi.org/10.1038/s41586-026-10916-7</a>","ieee":"M. A. Stouffer <i>et al.</i>, “Temporal uncoupling of radial glia lineage progression in cortical organoids,” <i>Nature</i>. Springer Nature, 2026.","chicago":"Stouffer, Melissa A, Osvaldo Miranda, Florian Pauler, Fabrizia Pipicelli, Carmen Streicher, Giselle T Cheung, and Simon Hippenmeyer. “Temporal Uncoupling of Radial Glia Lineage Progression in Cortical Organoids.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-026-10916-7\">https://doi.org/10.1038/s41586-026-10916-7</a>.","short":"M.A. Stouffer, O. Miranda, F. Pauler, F. Pipicelli, C. Streicher, G.T. Cheung, S. Hippenmeyer, Nature (2026)."},"status":"public","doi":"10.1038/s41586-026-10916-7","type":"journal_article","researchdata_availability":"yes","publication":"Nature","ec_funded":1,"OA_place":"publisher","publication_status":"epub_ahead","PlanS_conform":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ddc":["570"],"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"date_created":"2026-08-23T22:01:47Z","corr_author":"1","author":[{"first_name":"Melissa A","full_name":"Stouffer, Melissa A","id":"4C9372C4-F248-11E8-B48F-1D18A9856A87","last_name":"Stouffer"},{"orcid":"0000-0001-6618-6889","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","last_name":"Miranda","first_name":"Osvaldo","full_name":"Miranda, Osvaldo"},{"full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"id":"649134fd-d012-11ed-8f82-db1e5050f9ba","last_name":"Pipicelli","full_name":"Pipicelli, Fabrizia","first_name":"Fabrizia"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen"},{"full_name":"Cheung, Giselle T","first_name":"Giselle T","last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8457-2572"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon"}],"day":"12","date_published":"2026-08-12T00:00:00Z"}