Researchers map cancer cell trajectory in human glioblastoma tumours
Scientists have created a deep atlas of twelve human glioblastoma tumours to identify a specific cellular trajectory driving heterogeneity.
New atlas reveals cell paths
The study paired transcriptomic, epigenomic and genomic profiling across many regions within the twelve samples. Researchers found that heterogeneity arises from spatially patterned transitions of cancer cells. These transitions move cells from developmental-like states toward those defined by glial injury response and hypoxia.
Trajectory links to immune cells
The cellular trajectory is intimately linked to myeloid heterogeneity within the tissue. Tumour subclones are finely spatially intermixed through distinct regionalized myeloid signalling environments. This pattern manifests in a molecularly conserved manner across genetically distinct tumour subclones.
Validation using organoids and mutations
The team validated the findings using somatic mutation-based hierarchies in living models. They also used an experimental patient-derived organoid model for ex vivo testing. These methods confirmed the stereotyped trajectory of cancer cells in glioblastoma.
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