Evidence map›Paper›PMID 34059134›Full record

ArticleActa neuropathologica communications2021

Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches.

Sajina Shakya, Anthony D Gromovsky, James S Hale, Arnon M Knudsen, Briana Prager, Lisa C Wallace, Luiz O F Penalva, H Alex Brown, Bjarne W Kristensen, Jeremy N Rich and 3 more

Abstract read
In one paragraph

Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing 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

86 citing papers in PubMed.

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  12. Accumulation of Siglec10European journal of immunology · 2026
    Article
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26 more citing papers are in PubMed but not listed here.

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

13 authors.

Sajina ShakyaDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, ND2-4044195, USA.
Anthony D GromovskyCardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
James S HaleCardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Arnon M KnudsenDepartment of Pathology, Odense University Hospital, Odense, Denmark.
Briana PragerCleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA.
Lisa C WallaceDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, ND2-4044195, USA.
Luiz O F PenalvaChildren's Cancer Research Institute, University of Texas Health Sciences Center San Antonio, San Antonio, TX, USA.
H Alex BrownDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Bjarne W KristensenDepartment of Pathology, Odense University Hospital, Odense, Denmark.
Jeremy N RichDepartment of Medicine, University of Pittsburgh, Pittsburg, PA, USA.
Justin D LathiaCardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
J Mark BrownCardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Christopher G HubertDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, ND2-4044195, USA. hubertc@ccf.org.ORCID 0000-0002-1030-8549

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Targeting 15-PGDH in Colon Cancer Prognosis, Prediction, Treatment and PreventionP50CA150964 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARKOWITZ, SANFORD D. · 2011 to 2022
$24.6M
Project Two - Exercise Training Decreases Alcohol Drinking by an FGF21-Dependent MechanismP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI Thomas M McIntyre · 2016 to 2026
$19.6M
Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic diseaseP01HL147823 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Zeneng Wang · 2019 to 2026
$17.0M
Institutional Career Development CoreKL2TR002547 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI DWEIK, RAED A. · 2018 to 2022
$7.7M
Deciphering MDSC function for GBM targetingR01NS109742 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D., VOGELBAUM, MICHAEL A. · 2019 to 2023
$1.7M
Interaction between Tissue Factor, Junctional Adhesion Molecule-A, and Integrin B1 to drive self-renewal in glioblastomaR01NS117104 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HORBINSKI, CRAIG MICHAEL, LATHIA, JUSTIN D. · 2020 to 2024
$1.5M
Microbial metabolites and Innate Immunity in AH: Biomarkers of injury and repairU01AA026938 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI NAGY, LAURA E. · 2018 to 2023
$1.4M
Splicing factors and RNA processing alternations: exploring new players in glioblastoma developmentR21CA205475 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI PENALVA, LUIZ OTAVIO · 2016 to 2017
$365k
NCATS NIH HHS 4UL1TR000439NCATS NIH HHS KL2TR0002547NCATS NIH HHS UL1 TR000439NCI NIH HHS P30 CA043703NCI NIH HHS P50 CA150964NCI NIH HHS R21CA205475-01NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL120679NIAAA NIH HHS P50 AA024333NIAAA NIH HHS U01 AA026938NIGMS NIH HHS T32 GM007250NINDS NIH HHS R01 NS1089641NINDS NIH HHS R01 NS109742NINDS NIH HHS R01 NS117104
6 · The paper itself

Abstract

Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.

Indexed as

Brain NeoplasmsGlioblastomaHumansLipid MetabolismNeoplastic Stem CellsOrganoidsTumor Cells, CulturedTumor MicroenvironmentCancer stem cellGlioblastomaLipid dropletsOrganoidTumor heterogeneity

Identifiers

PMID34059134
PMCPMC8166002

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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.