Using an ML model trained on scRNA-seq profiles from our atlas, we found that over 50% of malignant GBM cells mapped to Tri-IPCs. Other malignant cells corresponded to cell types derivable from Tri-IPCs.

Interestingly, astrocyte-like, OPC-like, and inhibitory neuron-like tumor cells are also key components of glioblastoma multiforme (GBM), a devastating brain cancer. We wondered if similar processes might occur in GBM.

We named this cell population "Tr-IPC" to highlight their tri-potency. To confirm Tri-IPC’s tri-potency in vivo, we transplanted freshly isolated Tri-IPCs into neonatal mouse neocortex. Indeed, they still gave rise to astrocytes, OPCs, and inhibitory neurons.

Previous work showed that embryonic cortical neural stem cells can produce inhibitory neurons. Our study reveals they likely do so indirectly via a tri-potential progenitor cell that gives rise to astrocytes, OPCs, and inhibitory neurons.