Evidence map›Paper›PMID 35697781›Full record

ArticleNature cell biology2022

Enhanced cortical neural stem cell identity through short SMAD and WNT inhibition in human cerebral organoids facilitates emergence of outer radial glial cells.

Daniel Rosebrock, Sneha Arora, Naresh Mutukula, Rotem Volkman, Elzbieta Gralinska, Anastasios Balaskas, Amèlia Aragonés Hernández, René Buschow, Björn Brändl, Franz-Josef Müller and 3 more

Abstract read
In one paragraph

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Advances in three-dimensional modeling of ischemic injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Daniel Rosebrock *Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Sneha Arora *Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Naresh MutukulaDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Rotem VolkmanDepartment of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Elzbieta GralinskaDepartment of Computational Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID http://orcid.org/0000-0002-5876-7832
Anastasios BalaskasDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Amèlia Aragonés HernándezDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID http://orcid.org/0000-0003-1786-0595
René BuschowMicroscopy and Cryo-Electron Microscopy, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID http://orcid.org/0000-0002-9800-2578
Björn BrändlDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Franz-Josef MüllerDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID http://orcid.org/0000-0001-9478-8430
Peter F ArndtDepartment of Computational Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID http://orcid.org/0000-0003-1762-9836
Martin VingronDepartment of Computational Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID http://orcid.org/0000-0002-1765-4241
Yechiel ElkabetzDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany. elkabetz@molgen.mpg.de.ORCID http://orcid.org/0000-0002-3212-6463

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early Dual SMAD and WNT inhibition course is necessary and sufficient to establish robust and lasting cortical organoid NSC identity, efficiently suppressing non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC-specification capacity. Accordingly, this method selectively enriches for outer radial glia NSCs, which cyto-architecturally demarcate well-defined outer sub-ventricular-like regions propagating from superiorly radially organized, apical cortical rosette NSCs. Finally, this method culminates in the emergence of molecularly distinct deep and upper cortical layer neurons, and reliably uncovers cortex-specific microcephaly defects. Thus, a short SMAD and WNT inhibition is critical for establishing a rich cortical cell repertoire that enables mirroring of fundamental molecular and cyto-architectural features of cortical development and meaningful disease modelling.

Indexed as

Neural Stem CellsOrganoidsCell DifferentiationCerebral CortexEpendymoglial CellsHumansNeurogenesisNeurons

Identifiers

PMID35697781
PMCPMC9203281

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.