Evidence map›Paper›PMID 38016960›Full record

ArticleNature communications2023

Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity.

Anna Pagliaro, Roxy Finger, Iris Zoutendijk, Saskia Bunschuh, Hans Clevers, Delilah Hendriks, Benedetta Artegiani

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025
    Review
  15. Article
  16. Structural MRI of brain similarity networks.Nature reviews. Neuroscience · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Anna PagliaroThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0001-5221-7824
Roxy FingerThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0002-6048-8701
Iris ZoutendijkThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0003-4620-2962
Saskia BunschuhThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Hans CleversThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0002-3077-5582
Delilah HendriksThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands. d.hendriks@hubrecht.eu.ORCID 0000-0003-1159-5946
Benedetta ArtegianiThe Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands. b.a.artegiani@prinsesmaximacentrum.nl.ORCID 0000-0002-0904-4187
Princess Máxima Center · NLRoche (Switzerland) · CHRoyal Netherlands Academy of Arts and Sciences · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pluripotent stem cell (PSC)-derived human brain organoids enable the study of human brain development in vitro. Typically, the fate of PSCs is guided into subsequent specification steps through static medium switches. In vivo, morphogen gradients are critical for proper brain development and determine cell specification, and associated defects result in neurodevelopmental disorders. Here, we show that initiating neural induction in a temporal stepwise gradient guides the generation of brain organoids composed of a single, self-organized apical-out neuroepithelium, termed ENOs (expanded neuroepithelium organoids). This is at odds with standard brain organoid protocols in which multiple and independent neuroepithelium units (rosettes) are formed. We find that a prolonged, decreasing gradient of TGF-β signaling is a determining factor in ENO formation and allows for an extended phase of neuroepithelium expansion. In-depth characterization reveals that ENOs display improved cellular morphology and tissue architectural features that resemble in vivo human brain development, including expanded germinal zones. Consequently, cortical specification is enhanced in ENOs. ENOs constitute a platform to study the early events of human cortical development and allow interrogation of the complex relationship between tissue architecture and cellular states in shaping the developing human brain.

Indexed as

BrainPluripotent Stem CellsCell DifferentiationEmbryonic DevelopmentHumansNeurogenesisOrganoids

Identifiers

PMID38016960
PMCPMC10684874
OpenAlexW4389088346

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.