Evidence map›Paper›PMID 37384417›Full record

ArticleHuman molecular genetics2023

Cell-type specific defects in PTEN-mutant cortical organoids converge on abnormal circuit activity.

Martina Pigoni, Ana Uzquiano, Bruna Paulsen, Amanda J Kedaigle, Sung Min Yang, Panagiotis Symvoulidis, Xian Adiconis, Silvia Velasco, Rafaela Sartore, Kwanho Kim and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
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  4. Article
  5. Article
  6. Article
  7. Review
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  10. Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025
    Review
  11. Autism risk genes converge onbioRxiv : the preprint server for biology · 2025
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 1 country.

Martina PigoniDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Ana UzquianoDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Bruna PaulsenDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Amanda J KedaigleDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-6156-5046
Sung Min YangDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Panagiotis SymvoulidisMcGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Xian AdiconisStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Silvia VelascoDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Rafaela SartoreDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Kwanho KimDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Ashley TucewiczDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Sarah Yoshimi TroppDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Kalliopi TsafouStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xin JinDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Lindy BarrettDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Fei ChenDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Edward S BoydenMcGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joshua Z LevinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Paola ArlottaDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0003-2184-2277
Broad Institute · USHarvard University · USHoward Hughes Medical Institute · USMcGovern Institute for Brain Research · 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

De novo heterozygous loss-of-function mutations in phosphatase and tensin homolog (PTEN) are strongly associated with autism spectrum disorders; however, it is unclear how heterozygous mutations in this gene affect different cell types during human brain development and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type specific developmental events that are affected by heterozygous mutations in PTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep-layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes of PTEN heterozygosity that later converge on disrupted neuronal activity.

Indexed as

Autism Spectrum DisorderNeuronsCell DifferentiationHumansMutationOrganoidsPTEN PhosphohydrolasePTEN PhosphohydrolasePTEN protein, human

Identifiers

PMID37384417
PMCPMC10481103
OpenAlexW4382536313

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.