CHRDL1 Regulates Stemness in Glioma Stem-like Cells.
Inka K BerglarStephanie HehlgansAndrej WehleCaterina KleinChristel Herold-MendeFranz RödelDonat KögelBenedikt LinderPublished in: Cells (2022)
Glioblastoma (GBM) still presents as one of the most aggressive tumours in the brain, which despite enormous research efforts, remains incurable today. As many theories evolve around the persistent recurrence of this malignancy, the assumption of a small population of cells with a stem-like phenotype remains a key driver of its infiltrative nature. In this article, we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of bone morphogenic protein 4 (BMP4), which induces GSC differentiation and, hence, reduces tumorigenicity. We, therefore, employed two previously described GSCs spheroid cultures and depleted them of CHRDL1 using the stable transduction of a CHRDL1-targeting shRNA. We show with in vitro cell-based assays (MTT, limiting dilution, and sphere formation assays), Western blots, irradiation procedures, and quantitative real-time PCR that the depletion of the secreted BMP4 antagonist CHRDL1 prominently decreases functional and molecular stemness traits resulting in enhanced radiation sensitivity. As a result, we postulate CHRDL1 as an enforcer of stemness in GSCs and find additional evidence that high CHRDL1 expression might also serve as a marker protein to determine BMP4 susceptibility.
Keyphrases
- stem cells
- epithelial mesenchymal transition
- mesenchymal stem cells
- single cell
- bone regeneration
- binding protein
- protein protein
- real time pcr
- induced apoptosis
- amino acid
- high throughput
- high resolution
- gene expression
- risk assessment
- radiation induced
- climate change
- south africa
- white matter
- brain injury
- radiation therapy
- oxidative stress
- body composition
- bone mineral density
- mass spectrometry
- resting state
- liquid chromatography tandem mass spectrometry
- drug delivery
- cerebral ischemia
- functional connectivity
- simultaneous determination
- gas chromatography