Rxivist logo

Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics

By Teresa G Krieger, Stephan M. Tirier, Jeongbin Park, Tanja Eisemann, Heike Peterziel, Peter Angel, Roland Eils, Christian Conrad

Posted 07 May 2019
bioRxiv DOI: 10.1101/630202 (published DOI: 10.1093/neuonc/noaa091)

Glioblastoma multiforme (GBM) are devastating neoplasms with high invasive capacity. GBM has been difficult to study in vitro. Therapeutic progress is also limited by cellular heterogeneity within and between tumors. To address these challenges, we present an experimental model using human cerebral organoids as a scaffold for patient-derived glioblastoma cell invasion. By tissue clearing and confocal microscopy, we show that tumor cells within organoids extend a network of long microtubes, recapitulating the in vivo behavior of GBM. Single-cell RNA-seq of GBM cells before and after co-culture with organoid cells reveals transcriptional changes implicated in the invasion process that are coherent across patient samples, indicating that GBM cells reactively upregulate genes required for their dispersion. Functional therapeutic targets are identified by an in silico receptor-ligand pairing screen detecting potential interactions between GBM and organoid cells. Taken together, our model has proven useful for studying GBM invasion and transcriptional heterogeneity in vitro, with applications for both pharmacological screens and patient-specific treatment selection at a time scale amenable to clinical practice.

Download data

  • Downloaded 1,506 times
  • Download rankings, all-time:
    • Site-wide: 11,363
    • In cancer biology: 228
  • Year to date:
    • Site-wide: 74,517
  • Since beginning of last month:
    • Site-wide: 57,955

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)