Evidence map›Paper›PMID 37573007›Full record

ArticleBiological psychiatry2024

Loss of Function in the Neurodevelopmental Disease and Schizophrenia-Associated Gene CYFIP1 in Human Microglia-like Cells Supports a Functional Role in Synaptic Engulfment.

Steven D Sheridan, Joy E Horng, Hana Yeh, Liam McCrea, Jennifer Wang, Ting Fu, Roy H Perlis

Open access · greenAbstract read
In one paragraph

Article in Biological psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  2. Review
  3. Review
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  5. Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
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  8. Identifying brain-penetrant small-molecule modulators of human microglia using a cellular model of synaptic pruning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
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  10. Article
  11. 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

7 authors at 1 institution in 1 country.

Steven D SheridanCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Joy E HorngCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Hana YehCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Liam McCreaCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Jennifer WangCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Ting FuCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Roy H PerlisCenter for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: rperlis@mgh.harvard.edu.
Harvard University · US

Funding

Patient-derived Models of Synaptic Pruning in SchizophreniaR01MH120227 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI PERLIS, ROY H. · 2019 to 2023
$3.1M
Characterization of schizophrenia liability genes in models of human microglial synaptic pruningR01MH131687 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI ROY H. Perlis, Steven D Sheridan · 2023 to 2026
$2.4M
NIMH NIH HHS R01 MH120227NIMH NIH HHS R01 MH131687
6 · The paper itself

Abstract

backgroundThe CYFIP1 gene, located in the neurodevelopmental risk locus 15q11.2, is highly expressed in microglia, but its role in human microglial function as it relates to neurodevelopment is not well understood.

methodsWe generated multiple CRISPR (clustered regularly interspaced short palindromic repeat) knockouts of CYFIP1 in patient-derived models of microglia to characterize function and phenotype. Using microglia-like cells reprogrammed from peripheral blood mononuclear cells, we quantified phagocytosis of synaptosomes (isolated and purified synaptic vesicles) from human induced pluripotent stem cell (iPSC)-derived neuronal cultures as an in vitro model of synaptic pruning. We repeated these analyses in human iPSC-derived microglia-like cells derived from 3 isogenic wild-type/knockout line pairs derived from 2 donors and further characterized microglial development and function through morphology and motility.

resultsCYFIP1 knockout using orthogonal CRISPR constructs in multiple patient-derived cell lines was associated with a statistically significant decrease in synaptic vesicle phagocytosis in microglia-like cell models derived from both peripheral blood mononuclear cells and iPSCs. Morphology was also shifted toward a more ramified profile, and motility was significantly reduced. However, iPSC-CYFIP1 knockout lines retained the ability to differentiate to functional microglia.

conclusionsThe changes in microglial phenotype and function due to the loss of function of CYFIP1 observed in this study implicate a potential impact on processes such as synaptic pruning that may contribute to CYFIP1-related neurodevelopmental disorders. Investigating risk genes in a range of central nervous system cell types, not solely neurons, may be required to fully understand the way in which common and rare variants intersect to yield neuropsychiatric disorders.

Indexed as

Induced Pluripotent Stem CellsNeurodevelopmental DisordersSchizophreniaAdaptor Proteins, Signal TransducingHumansLeukocytes, MononuclearMicrogliaAdaptor Proteins, Signal TransducingCYFIP1 protein, human15q11.2AutismCYFIP1MicrogliaSchizophreniaSynaptic engulfment

Identifiers

PMID37573007
PMCPMC10874584
OpenAlexW4385728050

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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.