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Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1 [GBM]

ABSTRACT: Cancer research has largely focused on understanding mutations driving uncontrolled growth, leaving the organization of cellular hierarchies that sustain tumor progression less explored. We address this gap with ptalign, a tool that decodes such hierarchies in glioblastoma. By introducing the concept of pseudolineages mirroring adult neural stem cell lineages, we establish a correspondence between tumor pseudolineage and patient survival, devising biomarkers enabling cost-effective pseudolineage-based patient stratification. Comparing tumor pseudolineages to adult neural stem cell lineages, we identify the recurrent loss of the secreted Wnt antagonist SFRP1 in glioblastoma. This Wnt antagonist is expressed after the transition from dormant to quiescent neural stem cells, regulating their activation. Introducing SFRP1 into glioblastoma induced the generation of dormant astrocyte-like tumor cells, thereby increasing the quiescent tumor cell fraction and suggesting its potential as a target to arrest tumor progression. The insights facilitated by ptalign offer a new perspective on glioblastoma's cellular organization, providing a framework for understanding and treating glioblastomas and other solid tumors.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE240675 | GEO | 2023/12/01

REPOSITORIES: GEO

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