Evidence map›Paper›PMID 33619405›Full record

ArticleNature neuroscience2021

Long-term maturation of human cortical organoids matches key early postnatal transitions.

Aaron Gordon, Se-Jin Yoon, Stephen S Tran, Christopher D Makinson, Jin Young Park, Jimena Andersen, Alfredo M Valencia, Steve Horvath, Xinshu Xiao, John R Huguenard and 2 more

Abstract read
In one paragraph

Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
231citing papers in PubMed, 5 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

231 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Review
  8. GLP-1R agonist semaglutide protects human forebrain organoids from cholesterol-induced neurotoxicity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  9. Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026
    Review
  10. Review
  11. Article
  12. Article
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  14. Review
  15. Article
  16. Article
  17. β-Hydroxybutyrate Exposure is Associated with Increased THCellular and molecular neurobiology · 2026
    Article
  18. Review
  19. Article
  20. Article

171 more citing papers are in PubMed but not listed here.

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

12 authors.

Aaron GordonDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Se-Jin YoonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8412-5991
Stephen S TranDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Christopher D MakinsonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1427-8148
Jin Young ParkDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Jimena AndersenDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Alfredo M ValenciaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Steve HorvathDepartment of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4110-3589
Xinshu XiaoDepartment of Integrative Biology, University of California Los Angeles, Angeles, CA, USA.
John R HuguenardDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6950-1191
Sergiu P PașcaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. spasca@stanford.edu.ORCID http://orcid.org/0000-0002-3216-3248
Daniel H GeschwindDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. dhg@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-2896-3450

Funding

UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peyman Golshani, SUMA JACOB · 2020 to 2026
$9.6M
Inhibitory Controls of Thalamic NeuronsR01NS034774 · NINDS · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 1996 to 2021
$5.5M
1/2 Cross modal integration of molecular and physiological networks in ASDU01MH115746 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H, MEHTA, MAYANK R · 2017 to 2021
$5.3M
Cross modal integration of molecular and physiological networks in ASD (2/2)U01MH115745 · NIMH · STANFORD UNIVERSITY · PI PASCA, SERGIU · 2017 to 2021
$4.0M
Validation and optimization of epigenetic clocksU01AG060908 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2018 to 2022
$3.4M
Systematic approaches to deciphering regulation and function of RNA editing in brainR01MH123177 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI XIAO, XINSHU GRACE · 2021 to 2025
$3.1M
Chronic Axon Hypofunction in Maternal Immune Activation Models of Neurodevelopmental DisordersR01MH121075 · NIMH · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 2020 to 2023
$1.9M
Voltage-gated sodium channel regulation of neocortical developmentR00NS104215 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAKINSON, CHRISTOPHER DONALD · 2020 to 2022
$744k
NIA NIH HHS U01 AG060908NICHD NIH HHS P50 HD103557NIMH NIH HHS R01 MH121075NIMH NIH HHS R01 MH123177NIMH NIH HHS U01 MH115745NIMH NIH HHS U01 MH115746NINDS NIH HHS R00 NS104215NINDS NIH HHS R01 NS034774
6 · The paper itself

Abstract

Human stem-cell-derived models provide the promise of accelerating our understanding of brain disorders, but not knowing whether they possess the ability to mature beyond mid- to late-fetal stages potentially limits their utility. We leveraged a directed differentiation protocol to comprehensively assess maturation in vitro. Based on genome-wide analysis of the epigenetic clock and transcriptomics, as well as RNA editing, we observe that three-dimensional human cortical organoids reach postnatal stages between 250 and 300 days, a timeline paralleling in vivo development. We demonstrate the presence of several known developmental milestones, including switches in the histone deacetylase complex and NMDA receptor subunits, which we confirm at the protein and physiological levels. These results suggest that important components of an intrinsic in vivo developmental program persist in vitro. We further map neurodevelopmental and neurodegenerative disease risk genes onto in vitro gene expression trajectories to provide a resource and webtool (Gene Expression in Cortical Organoids, GECO) to guide disease modeling.

Indexed as

Cell DifferentiationDNA MethylationGene Regulatory NetworksHumansInduced Pluripotent Stem CellsIn Vitro TechniquesNeurodegenerative DiseasesOrganoids

Identifiers

PMID33619405
PMCPMC8109149

What OpenQuestion holds

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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.