---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22753'
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.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
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).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Melissa A
  full_name: Stouffer, Melissa A
  id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
  last_name: Stouffer
- first_name: Osvaldo
  full_name: Miranda, Osvaldo
  id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
  last_name: Miranda
  orcid: 0000-0001-6618-6889
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Fabrizia
  full_name: Pipicelli, Fabrizia
  id: 649134fd-d012-11ed-8f82-db1e5050f9ba
  last_name: Pipicelli
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Giselle T
  full_name: Cheung, Giselle T
  id: 471195F6-F248-11E8-B48F-1D18A9856A87
  last_name: Cheung
  orcid: 0000-0001-8457-2572
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
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>
  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>
  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>.
  ieee: M. A. Stouffer <i>et al.</i>, “Temporal uncoupling of radial glia lineage
    progression in cortical organoids,” <i>Nature</i>. Springer Nature, 2026.
  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.
  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>.
  short: M.A. Stouffer, O. Miranda, F. Pauler, F. Pipicelli, C. Streicher, G.T. Cheung,
    S. Hippenmeyer, Nature (2026).
corr_author: '1'
das_tickbox: '1'
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.
date_created: 2026-08-23T22:01:47Z
date_published: 2026-08-12T00:00:00Z
date_updated: 2026-09-07T13:29:07Z
day: '12'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41586-026-10916-7
ec_funded: 1
external_id:
  pmid:
  - '42587153'
file:
- access_level: open_access
  checksum: 11383e28fc430b28d2666f73833e8b56
  content_type: application/pdf
  creator: dernst
  date_created: 2026-09-07T13:24:10Z
  date_updated: 2026-09-07T13:24:10Z
  file_id: '22844'
  file_name: 2026_Nature_Stouffer.pdf
  file_size: 48513068
  relation: main_file
  success: 1
file_date_updated: 2026-09-07T13:24:10Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
  grant_number: F7805
  name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
    Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Temporal uncoupling of radial glia lineage progression in cortical organoids
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...