Work

Olig1/2 Orchestrates Progenitor Cell Fates during Mammalian Cortical Gliogenesis and Gliomagenesis

Year: 2025

Type: article

Abstract: The hijacking of developmental gliogenesis programs is a hallmark of glioblastoma (GBM), in which glial precursor cells (GPCs) typically differentiate into both neurons and glial cells. In GBM, this process is disrupted, leading to the overproduction of proliferative glial-like cells. Our study demonstrates that the knockout of Olig1/2 in both normal development and gliomagenesis causes GPCs to shift from generating highly proliferative oligodendrocyte precursor cells to producing non-proliferative olfactory bulb interneurons. Mechanistically, Olig1/2 play dual roles by orchestrating distinct transcriptional programs in GPCs, particularly inhibiting the expression of Gsx2 through direct binding to its multiple enhancers. Additionally, we provide compelling evidence that human H3.3G34R/V-mutant tumors, a subtype of high-grade gliomas, originate from dorsal cortical-derived GPCs rather than from the previously assumed progenitors in the ventral basal ganglia. Collectively, our findings reveal a previously unrecognized role of Olig1/2 in both gliogenesis and gliomagenesis, offering deeper insights into the connections between normal neural development and tumorigenesis. Graphical Abstract

Source: Nature Communications

DOI: 10.1038/s41467-025-64753-9