Evidence map›Paper›PMID 41413662›Full record

ArticleNature neuroscience2026

CRISPRi screening in cultured human astrocytes uncovers distal enhancers controlling genes dysregulated in Alzheimer's disease.

Nicole F O Green, Gavin J Sutton, Javier Pérez-Burillo, Juli Wang, Samuel Bagot, Hannah G Danon, Kieran Walsh, Akira Gokool, Samantha A Miles, Guang Yang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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.

Nicole F O Green *School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-7790-9077
Gavin J Sutton *School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Javier Pérez-BurilloSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Juli WangSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-2034-1107
Samuel BagotSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Hannah G DanonSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Kieran WalshSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Akira GokoolSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Samantha A MilesSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Guang YangSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-4377-1836
Charles A HerringHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.ORCID http://orcid.org/0000-0001-7620-5772
Yuheng LiangBioMedical Machine Learning Lab, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales, Australia.
Grant PfundsteinSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0009-0009-8490-1028
Vladimir SytnykSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1927-2199
Hamid Alinejad-RoknyBioMedical Machine Learning Lab, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales, Australia.
Ryan ListerHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.ORCID http://orcid.org/0000-0001-6637-7239
Joseph RosenbluhCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-9815-8049
Johann A Gagnon-BartschDepartment of Statistics, University of Michigan, Ann Arbor, MI, USA.
Irina VoineaguSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia. i.voineagu@unsw.edu.au.ORCID http://orcid.org/0000-0003-4162-3872

Funding

Department of Health | National Health and Medical Research Council (NHMRC) 2020814
6 · The paper itself

Abstract

Genetic variants associated with complex traits often lie in distal enhancers. While candidate enhancers have been mapped genome wide, their functional state and gene targets in specific cell types remain unclear. Here we present AstroREG, a resource of enhancer-gene interactions in human primary astrocytes, generated by combining CRISPR inhibition (CRISPRi), single-cell RNA-seq and machine learning. By functionally testing nearly 1,000 PsychENCODE enhancers, we identified more than 150 regulatory interactions, revealing enhancers that control key astrocyte functions and genes implicated in Alzheimer's disease. The CRISPRi screen also provided valuable ground-truth data from a primary cell type for training and benchmarking prediction models of enhancer activity. We thus developed EGrf, a random forest (RF) model trained on these data, and applied it genome wide to predict regulatory interactions with high specificity. Together, our data provide a comprehensive functional map of enhancer-mediated regulation in a key glial cell type, shedding light on brain function and disease.

Indexed as

Alzheimer DiseaseAstrocytesClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsEnhancer Elements, GeneticCells, CulturedHumansMachine LearningSingle-Cell Analysis

Identifiers

PMID41413662
PMCPMC12971484

What OpenQuestion 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 OpenQuestion graph.