Evidence map›Paper›PMID 27888226›Full record

ArticleMolecular systems biology2016

Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas.

Sören Müller, Siyuan John Liu, Elizabeth Di Lullo, Martina Malatesta, Alex A Pollen, Tomasz J Nowakowski, Gary Kohanbash, Manish Aghi, Arnold R Kriegstein, Daniel A Lim and 1 more

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
8.7field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 111 citations in OpenAlex.

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  19. Advancement of Single-Cell Sequencing in Medulloblastoma.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  20. Article

9 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

11 authors at 2 institutions in 1 country.

Sören MüllerDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Siyuan John LiuDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Elizabeth Di LulloEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Martina MalatestaDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Alex A PollenEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Tomasz J NowakowskiEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Gary KohanbashDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Manish AghiDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Arnold R KriegsteinEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Daniel A LimDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA daniel.lim@ucsf.edu aaron.diaz@ucsf.edu.ORCID http://orcid.org/0000-0001-7221-3425
Aaron DiazDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA daniel.lim@ucsf.edu aaron.diaz@ucsf.edu.ORCID http://orcid.org/0000-0001-9059-9501
University of California, San Francisco · USSan Francisco VA Medical Center · US

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Development and Expansion of the Human Cerebral CortexR35NS097305 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD · 2017 to 2024
$8.5M
Mapping the Developing Human Neocortex by Massively Parallel Single Cell AnalysisU01MH105989 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD · 2014 to 2016
$5.1M
Tumor cell and microenvironment changes causing antiangiogenic therapy resistanceR01NS079697 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2013 to 2021
$3.2M
Stem Cells of the Developing Human NeocortexR01NS075998 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD · 2011 to 2016
$1.8M
Long noncoding RNA regulation of neural stem cellsR01NS091544 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, DANIEL A · 2016 to 2020
$1.7M
Role of MLL Chromatin Remodeling Factor in Neural Stem CellsI01BX000252 · VA · VETERANS AFFAIRS MED CTR SAN FRANCISCO · PI DANIEL A LIM · 2009 to 2026
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BLRD VA I01 BX000252NCI NIH HHS P50 CA097257NIMH NIH HHS U01 MH105989NINDS NIH HHS R01 NS075998NINDS NIH HHS R01 NS079697NINDS NIH HHS R01 NS091544NINDS NIH HHS R35 NS097305
6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in GBM However, clinical trials of tyrosine-kinase inhibitors have shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single-cell expression profiles to sequentially acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. Descending the phylogenetic tree of a PDGF-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type, expressing pro-angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed an up-regulation of pro-invasive genes. An in-frame deletion in a specific dimerization domain of PDGF receptor correlates with an up-regulation of growth pathways in a proneural GBM and enhances proliferation when ectopically expressed in glioma cell lines. In-frame deletions in this domain are frequent in public GBM data.

Indexed as

Brain NeoplasmsErbB ReceptorsGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksGenetic HeterogeneityGlioblastomaHumansMutationReceptors, Platelet-Derived Growth FactorSequence Analysis, RNASingle-Cell AnalysisEGFR protein, humanErbB ReceptorsReceptors, Platelet-Derived Growth Factorcopy‐number variationglioblastomaPDGFRAsingle‐cell RNA‐sequencingtumor phylogeny

Identifiers

PMID27888226
PMCPMC5147052
OpenAlexW2555756186

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.