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Record W4285796970 · doi:10.1038/s41467-022-31408-y

A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours

2022· article· en· W4285796970 on OpenAlexafffund
Akram A. Hamed, Daniel J. Kunz, Ibrahim El-Hamamy, Quang M. Trinh, Omar Subedar, Laura M. Richards, Warren D. Foltz, Garrett Bullivant, Matthaeus Ware, Maria Vladoiu, Jiao Zhang, Antony M. Raj, Trevor J. Pugh, Michael D. Taylor, Sarah A. Teichmann, Lincoln Stein, Benjamin D. Simons, Peter B. Dirks

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health NetworkSickKids FoundationHospital for Sick ChildrenOntario Institute for Cancer Research
FundersMedical Research CouncilStand Up To CancerEntertainment Industry FoundationUniversity of TorontoCanadian Institutes of Health ResearchRoyal SocietyGovernment of CanadaWellcome TrustOntario Institute for Cancer ResearchHospital for Sick ChildrenSick Kids FoundationGenome CanadaGovernment of OntarioAmerican Association for Cancer Research
KeywordsAtlas (anatomy)NeuroscienceBiologyAnatomy

Abstract

fetched live from OpenAlex

Human cerebral cancers are known to contain cell types resembling the varying stages of neural development. However, the basis of this association remains unclear. Here, we map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on >100,000 cells. By comparing this reference atlas to single-cell data from >100 glial tumours of the adult and paediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that prenatal transformation of RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.000

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.294
Teacher spread0.278 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations35
Published2022
Admission routes2
Has abstractyes

Explore more

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