Evidence map›Paper›PMID 34969984›Full record

ArticleNature methods2022

Lineage recording in human cerebral organoids.

Zhisong He, Ashley Maynard, Akanksha Jain, Tobias Gerber, Rebecca Petri, Hsiu-Chuan Lin, Malgorzata Santel, Kevin Ly, Jean-Samuel Dupré, Leila Sidow and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Nature methods, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 1 pooled it
11.2field-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

117 citing papers in PubMed, 1 synthesis or guideline pooled it, 192 citations in OpenAlex.

  1. Pooled it
  2. Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026
    Review
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  4. Article
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  7. Article
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  10. Article
  11. Article
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  13. Article
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  15. Article
  16. Article
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  18. Progress and challenges in the development of advanced pancreatic cancer organoids.Journal of experimental & clinical cancer research : CR · 2026
    Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Zhisong He *Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1502-4801
Ashley Maynard *Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3588-3080
Akanksha Jain *Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0003-4704-7992
Tobias Gerber *Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0001-8456-5495
Rebecca PetriDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Hsiu-Chuan LinDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Malgorzata SantelDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Kevin LyDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0003-4714-1874
Jean-Samuel DupréDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3708-0425
Leila SidowMax Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0003-1246-7225
Fatima Sanchis CallejaDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-8461-2068
Sophie M J JansenDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Stephan RiesenbergMax Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0001-8171-1717
J Gray CampInstitute of Molecular and Clinical Ophthalmology, Basel, Switzerland. jarrettgrayson.camp@unibas.ch.ORCID http://orcid.org/0000-0003-3295-1225
Barbara TreutleinDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. barbara.treutlein@bsse.ethz.ch.ORCID http://orcid.org/0000-0002-3299-5597
ETH Zurich · CHMax Planck Institute for Evolutionary Anthropology · DEUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of cell states within these systems; however, approaches are needed to directly measure lineage relationships. Here we establish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR-Cas9 scarring and is compatible with single-cell and spatial transcriptomics. We apply iTracer to explore clonality and lineage dynamics during cerebral organoid development and identify a time window of fate restriction as well as variation in neurogenic dynamics between progenitor neuron families. We also establish long-term four-dimensional light-sheet microscopy for spatial lineage recording in cerebral organoids and confirm regional clonality in the developing neuroepithelium. We incorporate gene perturbation (iTracer-perturb) and assess the effect of mosaic TSC2 mutations on cerebral organoid development. Our data shed light on how lineages and fates are established during cerebral organoid formation. More broadly, our techniques can be adapted in any iPSC-derived culture system to dissect lineage alterations during normal or perturbed development.

Indexed as

Genes, ReporterCell LineageCerebral CortexCRISPR-Cas SystemsHumansInduced Pluripotent Stem CellsMicroscopyMutationNeuronsOrganoidsRecombinant ProteinsSequence Analysis, RNASingle-Cell AnalysisTuberous Sclerosis Complex 2 ProteinRecombinant ProteinsTSC2 protein, humanTuberous Sclerosis Complex 2 Protein

Identifiers

PMID34969984
PMCPMC8748197
OpenAlexW4200227839

What Socratic 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 Socratic graph.