Evidence map›Paper›PMID 39375777›Full record

ArticleGenome biology2024

In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma.

S John Liu, Christopher Zou, Joanna Pak, Alexandra Morse, Dillon Pang, Timothy Casey-Clyde, Ashir A Borah, David Wu, Kyounghee Seo, Thomas O'Loughlin and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Review
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  9. Probing neuropsychiatric disorders through in vivo CRISPR screening.Current opinion in genetics & development · 2026
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  10. Article
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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

17 authors.

S John LiuDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
Christopher ZouDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
Joanna PakDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
Alexandra MorseDepartment of Anatomy, University of California San Francisco, San Francisco, CA, 94143, USA.
Dillon PangDepartment of Anatomy, University of California San Francisco, San Francisco, CA, 94143, USA.
Timothy Casey-ClydeDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
Ashir A BorahArc Institute, Palo Alto, CA, 94304, USA.
David WuDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
Kyounghee SeoDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
Thomas O'LoughlinDepartment of Neuroscience, Icahn School of Medicine, Mount Sinai, New York, NY, 10029, USA.
Daniel A LimDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
Tomoko OzawaDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
Mitchel S BergerDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
Roarke A KamberDepartment of Anatomy, University of California San Francisco, San Francisco, CA, 94143, USA.
William A WeissDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
David R Raleigh *Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA. david.raleigh@ucsf.edu.
Luke A Gilbert *Arc Institute, Palo Alto, CA, 94304, USA. luke@arcinstitute.org.

Funding

Mechanisms of Hedgehog signaling in glioblastomaR01CA251221 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RALEIGH, DAVID R · 2021 to 2025
$2.6M
Systematic Discovery and Characterization of Novel Cancer Anti-Phagocytic MechanismsR00CA259218 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMBER, ROARKE ALEXANDER · 2023 to 2025
$637k
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NCI NIH HHS R00 CA259218NCI NIH HHS R01 CA251221NIH HHS S10 OD028511
6 · The paper itself

Abstract

backgroundGenetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking.

resultsHere, we iteratively develop a multiplex in vivo perturb-seq CRISPRi platform for single-cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery of sgRNA libraries into mouse models of GBM. Our platform enables potent silencing of drivers of in vivo growth and tumor maintenance as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune and stromal cells following in vivo CRISPRi perturbations that can affect tumor cell phagocytosis.

conclusionIn sum, we demonstrate the utility of multiplexed perturb-seq for in vivo single-cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.

Indexed as

Brain NeoplasmsGlioblastomaTumor MicroenvironmentAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceSingle-Cell AnalysisCancerCRISPRCRISPRiFunctional genomicsGBMGlioblastomaMicroenvironmentPerturb-seqRadiotherapy

Identifiers

PMID39375777
PMCPMC11457336

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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.