Evidence map›Paper›PMID 39983727›Full record

ArticleStem cell reports2025

An efficient, non-viral arrayed CRISPR screening platform for iPSC-derived myeloid and microglia models.

Sonja Meier, Anne Sofie Gry Larsen, Florian Wanke, Nicolas Mercado, Arianna Mei, Livia Takacs, Eva Suszanna Mracsko, Ludovic Collin, Martin Kampmann, Filip Roudnicky and 1 more

Abstract read
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  5. Review
  6. Article
  7. APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  8. Review
  9. Review
  10. Mapping microglial mechanisms in Alzheimer's disease: a comprehensive analysis.Experimental biology and medicine (Maywood, N.J.) · 2025
    Article
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

11 authors.

Sonja MeierPharma Research and Early Development, Neuroscience and Rare Diseases, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Anne Sofie Gry LarsenDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, England; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England.
Florian WankePharma Research and Early Development, Neuroscience and Rare Diseases, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Nicolas MercadoPharma Research and Early Development, Immunology and Inflammation, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Arianna MeiPharma Research and Early Development, Therapeutic Modalities, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Livia TakacsPharma Research and Early Development, Neuroscience and Rare Diseases, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Eva Suszanna MracskoPharma Research and Early Development, Neuroscience and Rare Diseases, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Ludovic CollinPharma Research and Early Development, Neuroscience and Rare Diseases, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Martin KampmannDepartment of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Filip RoudnickyPharma Research and Early Development, Therapeutic Modalities, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland. Electronic address: filip.roudnicky@roche.com.
Ravi JagasiaPharma Research and Early Development, Neuroscience and Rare Diseases, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Here, we developed a CRISPR-Cas9 arrayed screen to investigate lipid handling pathways in human induced pluripotent stem cell (iPSC)-derived microglia. We established a robust method for the nucleofection of CRISPR-Cas9 ribonucleoprotein complexes into iPSC-derived myeloid cells, enabling genetic perturbations. Using this approach, we performed a targeted screen to identify key regulators of lipid droplet formation dependent on Apolipoprotein E (APOE). We identify the Mammalian Target of Rapamycin Complex 1 (mTORC1) signaling pathway as a critical modulator of lipid storage in both APOE3 and APOE knockout microglia. This study is a proof of concept underscoring the utility of CRISPR-Cas9 technology in elucidating the molecular pathways of lipid dysregulation associated with Alzheimer's disease and neuroinflammation.

Indexed as

CRISPR-Cas SystemsInduced Pluripotent Stem CellsMicrogliaModels, BiologicalMyeloid CellsApolipoproteins ECell DifferentiationHumansLipid MetabolismMechanistic Target of Rapamycin Complex 1Signal TransductionApolipoproteins EMechanistic Target of Rapamycin Complex 1APOEarrayed genetic screeningCRISPR-Cas9 gene editingiPSC-derived microglialipid accumulationlipid droplet screenlipid metabolismlipid regulationlysosomemTORC1

Identifiers

PMID39983727
PMCPMC11960525

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.