Related Experiment Video
Updated: Jun 22, 2026
Derivation of Glial Restricted Precursors from E13 mice
Published on: June 20, 2012
PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrain
M C Assanah1, J N Bruce, S O Suzuki
1Department of Neurological Surgery, Columbia University, New York, New York 10032, USA.
Insights
Platelet-derived growth factor (PDGF) drives glioma formation by stimulating both PDGF-producing and neighboring glial progenitor cells. This highlights the critical role of paracrine signaling in malignant glioma growth and infiltration.
Area of Science:
- Neuroscience
- Oncology
- Cell Biology
Background:
- Platelet-derived growth factor (PDGF) is crucial for glial progenitor cell development.
- Aberrant PDGF signaling contributes to malignant glioma formation.
Purpose of the Study:
- To investigate the role of PDGF in glial progenitor cell behavior.
- To elucidate PDGF's contribution to glioma development and infiltration.
Main Methods:
- Neonatal rat pups' glial progenitor cells were infected with PDGF-expressing retroviruses.
- Tumor formation and cell migration were analyzed using microscopy and co-injection techniques.
- Exogenous PDGF was applied to slice cultures to assess progenitor cell responses.
Main Results:
- PDGF overexpression induced rapid proliferation and infiltration of glial progenitors, forming glioblastoma-like tumors.
- Both PDGF-producing and non-producing progenitors proliferated, indicating autocrine and paracrine signaling.
- Time-lapse microscopy confirmed high migratory and proliferative capacities of affected progenitors.
- Exogenous PDGF stimulated migration and proliferation in normal glial progenitors.
Conclusions:
- PDGF signaling is a key driver of malignant glioma formation.
- Glial progenitor cells exhibit inherent tumorigenic potential and growth factor responsiveness.
- Paracrine signaling plays a significant role in glioma growth and invasiveness.
Abstract:
Platelet-derived growth factor (PDGF) plays a major role in regulating migration, proliferation, and differentiation of glial progenitors during normal brain development and in the abnormal proliferation and dispersion that drives the formation of malignant gliomas. To further explore the relationship between PDGF's effects on normal glial progenitors and its role in the formation of gliomas, we infected progenitor cells in the subventricular zone (SVZ) of the lateral ventricle of neonatal rat pups with a retrovirus that expresses PDGF and green fluorescent protein (GFP). At 3 days post-injection (dpi), a proliferation of PDGFRalpha+ progenitors was seen in the SVZ and white matter around the injection site and by 10 dpi the animals had large diffusely infiltrating tumors that resembled glioblastomas. The tumors contained a massive proliferation of both infected and uninfected PDGFRalpha+ progenitors, suggesting that PDGF was driving tumor formation via both autocrine and paracrine signaling. Rats co-injected with two retroviruses (one that expresses PDGF-IRES-DSRED and one that expresses only GFP) formed tumors that contained a mixture of DSRED+ cells (PDGF producers) and GFP+ cells (recruited progenitors). Time-lapse microscopy of slice cultures confirmed that both DSRED+ and GFP+ cells were highly migratory and proliferative. Furthermore, adding exogenous PDGF to slice cultures generated from nontumor-bearing brains (injected with control GFP retrovirus only) stimulated the migration and proliferation of GFP+ progenitors. These findings reveal the inherent growth factor responsiveness and tumorigenic potential of PDGFRalpha+ progenitors and highlight the importance of paracrine signaling in stimulating glioma growth and infiltration.
