Evidence map›Paper›PMID 36179669›Full record

ArticleCell2022

Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex.

Ana Uzquiano, Amanda J Kedaigle, Martina Pigoni, Bruna Paulsen, Xian Adiconis, Kwanho Kim, Tyler Faits, Surya Nagaraja, Noelia Antón-Bolaños, Chiara Gerhardinger and 9 more

Open access · greenAbstract read
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed, 1 pooled it
17.8field-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

140 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.

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  19. 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
  20. Article

80 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

19 authors at 2 institutions in 1 country.

Ana UzquianoDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Amanda J KedaigleDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Martina PigoniDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bruna PaulsenDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xian AdiconisStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kwanho KimDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tyler FaitsDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Surya NagarajaDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Noelia Antón-BolañosDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Chiara GerhardingerDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ashley TucewiczDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Evan MurrayBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xin JinDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA.
Jason BuenrostroDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Fei ChenDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Silvia VelascoDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Joshua Z LevinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Paola ArlottaDepartment of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: paola_arlotta@harvard.edu.
Broad Institute · USHarvard University · US

Funding

Genetic neuroscience: How human genes and alleles shape neuronal phenotypesU01MH115727 · NIMH · BROAD INSTITUTE, INC. · PI ARLOTTA, PAOLA, BABADI, MEHRTASH · 2017 to 2021
$20.8M
Res Support CoreP50MH094271 · NIMH · HARVARD UNIVERSITY · PI HENSCH, TAKAO K · 2011 to 2022
$18.6M
Modeling ASD-linked genetic mutations in 3D human brain organoidsR01MH112940 · NIMH · HARVARD UNIVERSITY · PI Paola Arlotta · 2018 to 2026
$5.2M
High throughput assaying of circuit activity and connectivity in brain organoidsRF1MH123977 · NIMH · HARVARD UNIVERSITY · PI ARLOTTA, PAOLA, BOYDEN, EDWARD S. · 2020 to 2020
$2.5M
Howard Hughes Medical InstituteNIMH NIH HHS P50 MH094271NIMH NIH HHS R01 MH112940NIMH NIH HHS RF1 MH123977NIMH NIH HHS U01 MH115727
6 · The paper itself

Abstract

Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids can be impaired by abnormal metabolic states. We present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We show that processes of cellular diversification correlate closely to endogenous ones, irrespective of metabolic state, empowering the use of this atlas to study human fate specification. We define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. The findings validate this comprehensive atlas of human corticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development.

Indexed as

Cerebral CortexOrganoidsCell DifferentiationHumansNeurogenesisNeuronsBrain organoidsCortical developmentIn vitro metabolismMultiomicsNeuronal diversitySingle cell RNA-seqSpatial transcriptomics

Identifiers

PMID36179669
PMCPMC9990683
OpenAlexW4297981002

What OpenQuestion holds

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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.