Evidence map›Paper›PMID 39653820›Full record

ArticleNature methods2025

Multiplexing cortical brain organoids for the longitudinal dissection of developmental traits at single-cell resolution.

Nicolò Caporale, Davide Castaldi, Marco Tullio Rigoli, Cristina Cheroni, Alessia Valenti, Sarah Stucchi, Manuel Lessi, Davide Bulgheresi, Sebastiano Trattaro, Martina Pezzali and 9 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–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

20 citing papers in PubMed.

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  15. Cell villages and Dirichlet modeling map human cell fitness genetics.bioRxiv : the preprint server for biology · 2025
    Article
  16. Review
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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

19 authors.

Nicolò Caporale *Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0001-8097-4320
Davide Castaldi *Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0002-9055-0801
Marco Tullio Rigoli *Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Cristina CheroniHuman Technopole, Milan, Italy.
Alessia ValentiDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Sarah StucchiDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Manuel LessiDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0001-9898-7605
Davide BulgheresiHuman Technopole, Milan, Italy.ORCID http://orcid.org/0000-0002-2108-3429
Sebastiano TrattaroHuman Technopole, Milan, Italy.ORCID http://orcid.org/0000-0002-3142-6747
Martina PezzaliDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0003-0273-7391
Alessandro VitrioloHuman Technopole, Milan, Italy.
Alejandro Lopez-TobonHuman Technopole, Milan, Italy.
Matteo BonfantiHuman Technopole, Milan, Italy.
Dario RiccaHuman Technopole, Milan, Italy.ORCID http://orcid.org/0000-0003-3509-9699
Katharina T SchmidInstitute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-7082-1099
Matthias HeinigInstitute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-5612-1720
Fabian J TheisInstitute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-2419-1943
Carlo Emanuele VillaHuman Technopole, Milan, Italy.
Giuseppe TestaDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. giuseppe.testa@fht.org.ORCID http://orcid.org/0000-0002-9104-0918

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dissecting human neurobiology at high resolution and with mechanistic precision requires a major leap in scalability, given the need for experimental designs that include multiple individuals and, prospectively, population cohorts. To lay the foundation for this, we have developed and benchmarked complementary strategies to multiplex brain organoids by pooling cells from different pluripotent stem cell (PSC) lines either during organoid generation (mosaic models) or before single-cell RNA sequencing (scRNA-seq) library preparation (downstream multiplexing). We have also developed a new computational method, SCanSNP, and a consensus call to deconvolve cell identities, overcoming current criticalities in doublets and low-quality cell identification. We validated both multiplexing methods for charting neurodevelopmental trajectories at high resolution, thus linking specific individuals' trajectories to genetic variation. Finally, we modeled their scalability across different multiplexing combinations and showed that mosaic organoids represent an enabling method for high-throughput settings. Together, this multiplexing suite of experimental and computational methods provides a highly scalable resource for brain disease and neurodiversity modeling.

Indexed as

BrainOrganoidsSingle-Cell AnalysisHumansPluripotent Stem CellsSequence Analysis, RNA

Identifiers

PMID39653820
PMCPMC11810796

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.