RT Journal Article
SR Electronic
T1 Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 630202
DO 10.1101/630202
A1 Teresa G Krieger
A1 Stephan M Tirier
A1 Jeongbin Park
A1 Tanja Eisemann
A1 Heike Peterziel
A1 Peter Angel
A1 Roland Eils
A1 Christian Conrad
YR 2019
UL http://biorxiv.org/content/early/2019/05/07/630202.abstract
AB 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.