Evidence map›Paper›PMID 34992269›Full record

ReviewNature protocols2022

Engineering brain assembloids to interrogate human neural circuits.

Yuki Miura, Min-Yin Li, Omer Revah, Se-Jin Yoon, Genta Narazaki, Sergiu P Pașca

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature protocols, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
15.8field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 173 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026
    Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Engineering brain organoids: from neurodevelopmental modeling to translational barriers.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Parabiosis, Assembloids, Organoids (PAO).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  20. Review

50 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

6 authors at 2 institutions in 1 country.

Yuki MiuraDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1410-3612
Min-Yin LiDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8102-632X
Omer RevahDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Se-Jin YoonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8412-5991
Genta NarazakiDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3063-2570
Sergiu P PașcaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. spasca@stanford.edu.ORCID http://orcid.org/0000-0002-3216-3248
Neurosciences Institute · USStanford University · US

Funding

Gaining insight into psychiatric disease by engineering piece by piece the human brain in vitro.R01MH107800 · NIMH · STANFORD UNIVERSITY · PI PASCA, SERGIU · 2015 to 2024
$5.6M
6 · The paper itself

Abstract

The development of neural circuits involves wiring of neurons locally following their generation and migration, as well as establishing long-distance connections between brain regions. Studying these developmental processes in the human nervous system remains difficult because of limited access to tissue that can be maintained as functional over time in vitro. We have previously developed a method to convert human pluripotent stem cells into brain region-specific organoids that can be fused and integrated to form assembloids and study neuronal migration. In contrast to approaches that mix cell lineages in 2D cultures or engineer microchips, assembloids leverage self-organization to enable complex cell-cell interactions, circuit formation and maturation in long-term cultures. In this protocol, we describe approaches to model long-range neuronal connectivity in human brain assembloids. We present how to generate 3D spheroids resembling specific domains of the nervous system and then how to integrate them physically to allow axonal projections and synaptic assembly. In addition, we describe a series of assays including viral labeling and retrograde tracing, 3D live imaging of axon projection and optogenetics combined with calcium imaging and electrophysiological recordings to probe and manipulate the circuits in assembloids. The assays take 3-4 months to complete and require expertise in stem cell culture, imaging and electrophysiology. We anticipate that these approaches will be useful in deciphering human-specific aspects of neural circuit assembly and in modeling neurodevelopmental disorders with patient-derived cells.

Indexed as

Nerve NetOrganoidsBrainCell Culture TechniquesCells, CulturedHumansMolecular ImagingNeurophysiologyOptogeneticsOrgan Culture TechniquesPluripotent Stem Cells

Identifiers

PMID34992269
OpenAlexW4206328973

What OpenQuestion holds

Textmetadata
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.