Evidence map›Paper›PMID 35122077›Full record

ArticleNature cancer2021

Gradient of Developmental and Injury Response transcriptional states defines functional vulnerabilities underpinning glioblastoma heterogeneity.

Laura M Richards, Owen K N Whitley, Graham MacLeod, Florence M G Cavalli, Fiona J Coutinho, Julia E Jaramillo, Nataliia Svergun, Mazdak Riverin, Danielle C Croucher, Michelle Kushida and 27 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.

0numbers the graph read from it
0cells of the map it votes in
183citing papers in PubMed
24.1field-weighted citation impact, top 1% 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

183 citing papers in PubMed, 315 citations in OpenAlex.

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123 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 8 institutions in 2 countries.

Laura M Richards *Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-3414-7628
Owen K N Whitley *Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Graham MacLeodLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-6401-9307
Florence M G CavalliDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Fiona J CoutinhoDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Julia E JaramilloDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Nataliia SvergunDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Mazdak RiverinPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Danielle C CroucherDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Michelle KushidaDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Kenny YuDivision of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.
Paul GuilhamonDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Naghmeh RastegarDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Moloud AhmadiLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Jasmine K BhattiLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Danielle A BozekDepartment of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
Naijin LiDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lilian LeeDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Clare CheDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Erika LuisDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Nicole I ParkPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Zhiyu XuPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Troy KetelaPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Richard A MooreCanada's Michael Smith Genome Sciences Centre, British Columbia Cancer, Vancouver, British Columbia, Canada.
Marco A MarraCanada's Michael Smith Genome Sciences Centre, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-7146-7175
Julian SpearsDivision of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.
Michael D CusimanoDivision of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.
Sunit DasDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-2146-4168
Mark BernsteinDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Benjamin Haibe-KainsDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Mathieu LupienDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
H Artee LuchmanDepartment of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
Samuel WeissDepartment of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
Stephane AngersLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-7241-9044
Peter B DirksDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. peter.dirks@sickkids.ca.ORCID http://orcid.org/0000-0001-5718-6465
Gary D BaderDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. gary.bader@utoronto.ca.ORCID http://orcid.org/0000-0003-0185-8861
Trevor J PughDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. trevor.pugh@utoronto.ca.ORCID http://orcid.org/0000-0002-8073-5888
Hospital for Sick Children · CAUniversity of Toronto · CAUniversity Health Network · CASt. Michael's Hospital · CAOntario Institute for Cancer Research · CAUniversity of Calgary · CACanada's Michael Smith Genome Sciences Centre · CAUniversity of British Columbia · CA

Funding

CIHR
6 · The paper itself

Abstract

Glioblastomas harbor diverse cell populations, including rare glioblastoma stem cells (GSCs) that drive tumorigenesis. To characterize functional diversity within this population, we performed single-cell RNA sequencing on >69,000 GSCs cultured from the tumors of 26 patients. We observed a high degree of inter- and intra-GSC transcriptional heterogeneity that could not be fully explained by DNA somatic alterations. Instead, we found that GSCs mapped along a transcriptional gradient spanning two cellular states reminiscent of normal neural development and inflammatory wound response. Genome-wide CRISPR-Cas9 dropout screens independently recapitulated this observation, with each state characterized by unique essential genes. Further single-cell RNA sequencing of >56,000 malignant cells from primary tumors found that the majority organize along an orthogonal astrocyte maturation gradient yet retain expression of founder GSC transcriptional programs. We propose that glioblastomas grow out of a fundamental GSC-based neural wound response transcriptional program, which is a promising target for new therapy development.

Indexed as

Brain NeoplasmsGlioblastomaCarcinogenesisHumansNeoplastic Stem Cells

Identifiers

PMID35122077
OpenAlexW3119492369

What OpenQuestion holds

Textmetadata
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.