METB-08. Unraveling the cellular diversity and spatial architecture of infant-type hemispheric gliomas using multi-omic profiling
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract Infant-type hemispheric gliomas (IHGs) are rare receptor tyrosine kinase (RTK)-driven tumors with fusions in ALK, ROS1, MET, and NTRK genes. Aberrant RTK activation may interfere with normal neural development, derailing developing cells onto hyperproliferative and divergent trajectories. Key questions about tumor composition, cell of origin, and RTK fusion’s role in tumor formation remain unanswered. We analyzed a cohort of RTK-fused gliomas (n = 13 IHGs) using single-cell multi-omic RNA/ATAC-seq (n = 20) or SmartSeq2 (n = 7) and generated an atlas of over 90’000 transcriptomes and 1M spatially resolved cells. Integration with brain development datasets identified five progenitor-like cancer populations spanning a continuum of states: Radial glia-like, NPC/Neuronal-like, OPC-like, GPC/Astrocyte-like, and cycling. Trajectory analysis revealed a gradient of cancer cells expressing both developmental and mature brain lineage genes. RNA velocity pinpointed Radial glia-like cells as the likely origin, diverging into GPC/Astrocyte-like, NPC/Neuronal-like, and OPC-like lineages. RTK fusion-positive cells were identified across all cells, highlighting early progenitors as drivers of tumorigenesis. Interestingly, a higher proportion NPC/Neuronal-like cells was found in IHGs, suggesting an earlier oncogenic hit in those patients, and lacked MES-like tumor cells found in other gliomas. Chromatin analysis revealed dynamic accessibility changes and transcription factor motifs across cell populations. Radial-glia-like cells displayed open chromatin linked to undifferentiated cells, resembling the state of other cancers. Moreover, GPC/Astrocyte-like and NPC/Neuronal-like populations showed neurogenesis and synaptic function. Motif analysis identified lineage-defining factors and oncogenic regulators, illustrating the role of chromatin remodeling in plasticity and lineage specification. Finally, we mapped the spatial architecture using MERFISH in n = 4 IHGs and uncovered a heterogeneous spatial distribution of cell states. While lacking global structure, cancer cells exhibited higher spatial coherence and clustered into localized regions, suggesting tumor organization recapitulates aberrant brain morphogenesis. Taken together, our multi-omics atlas describes the cellular and spatial heterogeneity of IHGs, providing new insights into their developmental origins, unique biology, and clinical implications.
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.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it